The Journal for Equine Nutrition - Summer '22

suMMeR 2022 Issue The Journal for 5 Equine Nutrition ® Feedmark update on laminitis Professor Nicola Menzies-Gow, MA VetMB, PhD, DipECEIM, CertEM(Int.med), FHEA, FRCVS energy sources for performance horses Anouk Frieling, MSc, BSc (Hons) liver disease in horses Eduardo Alguacil, MRCVS equine plant toxicity: toxic metabolites, Rebecca Allan systems affected and management nutrient spotlight: turmeric Anouk Frieling, MSc, BSc (Hons) PB 1The Journal for Equine Nutrition is FREE. To get every edition of The JEN to your inbox for free, sign up today at feedmark.com/JEN You will receive no marketing literature, and you will be the first to receive The JEN! Editor Contact us Dr Stephanie Wood 01986 782368 [email protected] [email protected] Published by Contributors Feedmark Ltd, Harleston, Norfolk, IP20 0NY With special thanks to Anouk Frieling, Eduardo Alguacil, Professor Nicola Menzies-Gow and Rebecca Allan Whilst every care has been taken in compiling this publication The JEN shall not be made liable for any inaccuracies therein. Production & Design The opinions expressed in this publication are not necessarily Gemma Hill those of the Editor/Publisher. [email protected] 2 3Welcome I am delighted to bring you the summer issue of the provides an update on the causes, symptoms and treatment options for equine liver disease. As the liver has primary JEN. This is the 5th issue, meaning that the JEN has been metabolic functions, early diagnosis and veterinary supporting horse owners for over a year and is now an intervention are key to successful treatment of liver issues, established platform to communicate nutrition, veterinary making this article relevant to all owners. The next article and behavioural sciences. The JEN’s ability to translate builds on this knowledge, diving deep into the subject of technical information into practical advice in a reader plant toxicity which often affects the liver. Rebecca Allan, friendly format has been so well received by all involved Feedmark’s Assistant Nutritionist, explores the different in the equine industry and highlights its importance in toxins that can be found in plants commonly found in bridging the gap between research, and those who manage grazing or forage, and discusses the consequences of and care for horses, ponies, and donkeys. This issue builds their consumption on the horse’s health. Pictures of these on previous successes, focusing on subjects relevant to the common plants are included in an appendix to aid in warmer summer months. their identification. R Nicola Menzies-Gow, Professor of Equine Medicine EP The final article is an ingredient spotlight looking at the A at the Royal Veterinary College, writes the first article, P popular spice turmeric. Anouk Frieling explores turmeric’s D providing a timely Update on laminitis. Although grass E composition and how this influences its biological effects LC growth was slow to get going in the spring, the warm wet Y within the body. C weather of recent weeks has provided ideal conditions for ER I hope you will find the articles informative and pastures to flourish, increasing the risk of laminitis and %00 beneficial over the summer months and I look forward to making this article an important read for all. 1 N hearing your feedback. If you have any suggestions for O The second article on Energy sources for performance topics to be covered in future issues of the JEN please let DE horses written by Anouk Frieling, Feedmark’s Senior T me know by emailing [email protected] NI Nutritionist, outlines the different energy pathways and RP dietary options for supporting optimum performance and is relevant to horses with greater exercise demands. The next two articles have an equine health focus. Dr. Stephanie Wood Editor Eduardo Alguacil from Uplands Way Veterinary Clinics, CONTENTS 4 17 Update on laminitis Equine plant toxicity: toxic metabolites, internal systems affected and management 8 Energy sources for performance horses 26 Ingredient spotlight: Turmeric 13 Liver disease in horses 30 Glossary 2 3Update on laminitis Nicola Menzies-Gow, MA VetMB, PhD, DipECEIM, CertEM(Int.med), FHEA, FRCVS, Professor of Equine Medicine, Royal Veterinary College. Laminitis is now considered to be a syndrome associated failure in painful limb conditions such as fractures and with systemic disease (sepsis or endocrine disease) or joint/tendon sheath infections as laminitis develops in altered weight bearing rather than being a disease itself the contralateral limb due to excessive weight bearing. (Patterson-Kane et al., 2018). There are three forms of It is thought that the increased weight bearing results in laminitis, each of which occurs in association with very decreased blood supply to the foot as the blood supply is different diseases and occurs following very different reliant on movement to help pump it around the foot. The sequences of events in the body: decreased blood supply means that the delivery of oxygen and nutrients to the foot is reduced resulting in laminitis. SEPSIS-ASSOCIATED LAMINITIS Sepsis-associated laminitis occurs secondary to a severe SYMPTOMS OF LAMINITIS systemic (involving the whole body) inflammatory response The symptoms of laminitis are the same regardless of and/or sepsis (bacterial infection in the blood) and so type and include any combination of: occurs in animals with, for example, severe gastrointestinal • Lameness that usually affects two or more limbs, disease, pleuropneumonia (bacterial infection of the lungs but lameness in one limb is possible that has extended into the pleural space) and septic metritis • Reluctance to walk with a short, stilted gait and (bacterial infection of the uterus) following retention of the difficulty turning that is worse on hard ground placenta. Toxins produced by the bacteria are absorbed into • Increased (or bounding) digital pulses the blood stream where they set off a severe inflammatory • Increased hoof wall temperature reaction. Whilst there is evidence of inflammation in several • Weight shifting places throughout the body such as the skin (Riggs et al., • Pain on hoof tester pressure at the toe region just 2009), lungs and the liver (Stewart et al., 2009), the foot in front of the point of the frog appears to be most severely affected with laminitis being • Characteristic stance of leaning back on the heels the end result. and taking weight off the painful toe region • Palpable depression at the coronary band ENDOCRINOPATHIC LAMINITIS Endocrinopathic laminitis is the commonest form The lameness can vary in severity from that which is of laminitis, accounting for 90% of cases of laminitis in only perceptible at the trot, through to spending prolonged some studies (Karikoski et al., 2011). It includes laminitis periods recumbent. Some episodes of laminitis are associated with abnormal regulation of the hormone insulin (insulin dysregulation; ID), as occurs in equine metabolic syndrome (EMS) and in a subset of animals with pituitary pars intermedia dysfunction (PPID; equine Cushing’s disease) (Durham et al., 2019). Exactly how insulin causes laminitis has yet to be fully determined. The current theory with the most supporting evidence is that insulin binds to and activates the insulin like growth factor-1 (IGF-1) receptor in the lamellae resulting in laminitis. SUPPORTING LIMB LAMINITIS Supporting limb laminitis (SLL) is uncommon (Wylie et Figure 1. Divergent hoof growth rings are a sign of changes within the al., 2015). However, it is a major contributor to treatment hoof associated with laminitis. Credit: Professor Menzies-Gow 4 5subclinical and whilst there is no obvious lameness (or supporting-limb laminitis needs to be treated specifically. any other clinical sign), it subsequently becomes apparent Additionally, cryotherapy (cold therapy) is indicated in as divergent hoof growth rings (Patterson-Kane et al., certain circumstances. 2018) (Figure 1). PAIN RELIEF DIAGNOSIS OF LAMINITIS Non-steroidal anti-inflammatory drugs (NSAIDs) such A diagnosis of laminitis is usually based on the history, a flunixin and phenylbutazone (bute) are the first choice as it is often recurrent, and the clinical signs. X-rays are for pain relief and there is no evidence to suggest that taken in cases where rotation and/or sinking of the pedal any one specific NSAID is superior to the next (Menzies- bone within the hoof capsule is suspected. Gow et al., 2010). Although not a strong painkiller on its own, paracetamol appears to have an excellent effect in Further diagnostic tests are performed to identify the laminitic cases when used in addition to other NSAIDs presence of an underlying endocrine (hormone) disease (West et al., 2011). in suspect animals. A diagnosis of EMS is made based on demonstrating the presence of ID. Insulin dysregulation If NSAIDs do not provide enough pain relief, then can manifest in three ways and tests are required to identify opiates can be used in addition e.g., butorphanol, pethidine each manifestation. High circulating insulin concentrations and morphine. Fentanyl patches applied directly to the skin are detected by measuring blood insulin concentrations. can also be considered as it was found to be effective in Excessive release of insulin into the blood following R horses with pain refractory to NSAID analgesia in one small EP ingestion of carbohydrate is identified using an oral sugar clinical report (Thomasy et al., 2004). However, uptake of AP (OST) or glucose (OGT) test. An abnormal response of the fentanyl from a skin patch is highly variable in adult horses DEL tissues to insulin is detected using an intravenous insulin (Orsini et al., 2006). Tramadol has also been advocated as CY tolerance test. A diagnosis of PPID is made by measuring it decreased forelimb offloading in four cases of chronic CE blood concentrations of the pituitary-derived hormone R laminitis (Guedes et al., 2016), but current evidence does % adrenocorticotrophic hormone (ACTH) and/or using a 0 not support its use alone as it has a low absorption (~9%) 01 thyrotropin releasing hormone (TRH) stimulation test. from the gastrointestinal tract and it only lasts a very short NO time (~2 hours) (Stewart et al., 2011). TREATMENT DET If single drugs do not provide adequate analgesia, then Treatment involves providing pain relief and supporting NIR several drugs can be used in combination in the hospital the foot to prevent any/further movement of the pedal P setting. Possible combinations typically involve NSAID bone within the hoof. The underlying endocrine disease administration in combination with an intravenous infusion or primary condition causing sepsis-associated or Nicola Menzies-Gow, MA VetMB, PhD, DipECEIM, CertEM(Int. med), FHEA, FRCVS, Professor of Equine Medicine, Royal Veterinary College. Nicola graduated from Cambridge University in 1997 and worked for 3 years in a first opinion equine practice in Essex before joining the Royal Veterinary College (RVC) as a resident in equine medicine. After completing her residency, Nicola successfully gained a PhD in equine endotoxemia and became a Diplomat of the European College of Equine Internal Medicine. Nicola became a Lecturer in equine medicine at the RVC in 2005 and has been sequentially promoted to Professor. Her research interested focus on equine endocrinopathic laminitis. 4 5up to four other types of drugs. seen in the foot seen under a microscope in the experimental model of endocrinopathic laminitis when the cooling was A nerve-related component to the pain associated initiated at the same time as the insulin dysregulation with laminitis has been demonstrated, making the drugs was induced (Stokes et al., 2019). However, there are no ketamine and gabapentin potentially suitable drugs. In one published studies to date evaluating its use when initiated study, the combination of tramadol and ketamine resulted either after the onset of clinical signs in the experimental in decreased forelimb off-loading frequency and increased model of endocrinopathic laminitis or in naturally occurring forelimb loading in horses with naturally occurring laminitis cases of endocrinopathic laminitis. In addition, there is no (Guedes et al., 2012). Gabapentin improved hindlimb pain published evidence relating to the use of cryotherapy for that was probably associated with femoral nerve damage in treatment of supporting limb laminitis. one horse (Davis et al., 2007) and had no apparent adverse effects following oral administration in horses (Terry DIET et al., 2010). Animals with acute endocrinopathic laminitis should be removed from the pasture and box rested. A diet based The drug(s) that will provide sufficient pain relief in any on grass hay with low (<10%) non-structural carbohydrate individual horse is very variable and often it is a matter of (NSC) content should be fed, and cereals avoided. Ideally, trialling each drug to see the clinical response. the forage should be analysed before it is fed. Some FOOT SUPPORT recommend soaking hay in water for 60 minutes before Supporting the foot is essential. Additional support feeding to leach water soluble carbohydrates and so should be applied to the back two thirds of the foot to circumvent the need for analysis; however, this does not provide pain relief and to minimise the mechanical forces reliably decrease the NSC content to <10% in all cases on the laminae and hence prevent/reduce pedal bone (Longland et al., 2011). If absolutely necessary, some of movement. The simplest method is to increase the depth of the hay can be substituted with other fibre-based products the bedding, ensuring that the bedding extends to the door such as chaff and unmolassed sugar beet. Forage-only diets where the horse will spend most of its day. Alternatively, do not provide adequate protein, minerals, or vitamins, or additionally, extra support can be applied directly to the particularly if the hay is soaked; thus, a low-calorie foot itself using methods that can be broadly divided into commercial ration balancer product that contains high- frog only supports and combined frog and sole supports. quality protein and a mixture of vitamins and minerals There is no evidence to suggest that any one foot support is recommended. method is superior (Menzies-Gow et al., 2010). TREATMENT OF UNDERLYING ENDOCRINE CRYOTHERAPY DISEASE There is evidence to support the use of cryotherapy Additional therapies are indicated if an underlying (cold therapy) in the treatment of sepsis-associated endocrinopathy is confirmed. Treatment of EMS should laminitis. Continuous cooling of the foot was beneficial focus on management changes aimed at weight reduction if in experimentally-induced sepsis-associated laminitis the animal is overweight and improving insulin sensitivity in all animals. Weight reduction is achieved through when initiated after the onset of clinical signs of laminitis feeding a diet high in fibre and low in NSC. Grain and (van Eps et al., 2014) and prophylactic cryotherapy was other concentrated sources of calories should be removed associated with a decreased incidence of laminitis in horses from the diet. Hay or hay substitute should initially be with colitis (severe diarrhoea) (Kullmann et al., 2014). The provided at 1.5% of current body weight per day, with hoof temperature should be maintained at <10°C for 72 subsequent further reductions in feed amount depending on hours, which can most easily be achieved by immersing the the extent of weight loss. If weight loss is not sufficient foot and pastern region in strong plastic bags containing a despite feeding an appropriate diet, up to 30% of the hay slurry of ice and water that is then taped around the pastern. ration can be substituted with straw (Dosi et al., 2020). The Recently it has been demonstrated that cryotherapy food should be divided into several smaller feeds per day and strategies used to prolong feed intake time e.g., use reduced the severity of laminitis and prevented the changes 6 7of multiple hay nets with small holes, use of a hay bag, PREVENTION OF LAMINITIS suspending the hay net from the ceiling in the middle of SEPSIS-ASSOCIATED LAMINITIS the stable. A low glycemic diet should be fed to lean EMS Sepsis-associated laminitis is prevented through animals and to overweight animals that have reached their prompt and appropriate treatment of the diseases that it is target weight. The diet should be based on low NSC, high associated with. In addition, cryotherapy can be used in at- quality fibre with fat (oil) used to provide additional calories risk animals e.g., following colic surgery or animals with if required. A low-calorie protein/vitamin/mineral balancer severe diarrhoea. should be fed to all animals. Exercise also helps with weight loss and improves insulin sensitivity. The optimal ENDOCRINOPATHIC LAMINITIS amount of exercise required has yet to be determined, but Prevention of endocrinopathic laminitis relies on daily exercise once the laminitis has resolved is probably prompt recognition of the underlying endocrine disease best. If management changes alone are unsuccessful, and regulation of access to pasture as it appears that the then pharmacologic interventions involving metformin, laminitis is often triggered by pasture consumption. levothyroxine or SGLT-2 inhibitors (e.g., ertuglifozin) can Finally, efforts should be made to ensure that the individual be additionally used in the short term (3-6 months). animal remains at a healthy weight, as the risk of laminitis is increased in overweight/obese animals. The first-choice treatment for PPID is the drug pergolide. The initial dose is 2µg/kg p.o. SID for 4-6 weeks. The test SUPPORTING LIMB LAMINITIS used to make a diagnosis of PPID should then be repeated to Supporting limb laminitis is prevented by prompt RE determine how well the animal has responded to the therapy treatment of the initial predisposing lameness and PA alongside any changes in the clinical signs associated with P application of a foot support to the contralateral limb. D PPID such as lethargy and haircoat changes. Animals with Whilst movement is important to maintain the circulation to ELC PPID that also have ID will require management changes the foot, it often contraindicated due to the initial lameness. YC similar to those recommended for animals with EMS to Whilst limb movement may be possible through use of ER physiotherapy, the ideal duration or frequency is unknown. help improve sensitivity of the body to the hormone insulin. %001 REFERENCES N Davis, J.L., Posner, L.P., & Elce, Y. (2007). Gabapentin for the treatment of neuropathic pain in a pregnant horse. Journal of American Veterinary Medical Association, 231: 755-758. O Dosi, M.C.M., Kirton, R., Hallsworth, S., Keen, J.A., & Morgan, R.A. (2020). Inducing weight loss in native ponies: is straw a viable alternative to hay? Vet Record, 187: e60. Durham, A.E., Frank, N., McGowan, C.M., Menzies-Gow, N.J., Roelfsema, E., Vervuert, I., Feige, K., & Fey, K. (2019). ECEIM consensus statement on equine metabolic syndrome. Journal of Veterinary DE Internal Medicine, 33: 335-349. T Guedes, A., Knych, H., & Hood, D. (2016). Plasma concentrations, analgesic and physiological assessments in horses with chronic laminitis treated with two doses of oral tramadol. Equine Veterinary NI Journal, 48: 528-531. RP Guedes, A.G., Matthews, N.S., & Hood, D.M. (2012). Effect of ketamine hydrochloride on the analgesic effects of tramadol hydrochloride in horses with signs of chronic laminitis-associated pain. American Journal of Veterinary Research, 73: 610-619. Karikoski, N.P., Horn, I., McGowan, T.W., & McGowan, C.M. (2011). The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital. Domestic Animal Endocrinology, 41: 111-117. Kullmann, A., Holcombe, S.J., Hurcombe, S.D., Roessner, H.A., Hauptman, J.G., Geor, R.J., & Belknap, J. (2014). Prophylactic digital cryotherapy is associated with decreased incidence of laminitis in horses diagnosed with colitis. Equine Veterinary Journal, 46: 554-559. Longland, A.C., Barfoot, C., & Harris, P.A. (2011). Effects of soaking on the water-soluble carbohydrate and crude protein content of hay. Veterinary Record, 168: 618. Menzies-Gow, N.J., Stevens, K., Barr, A., Camm, I., Pfeiffer, D., & Marr, C.M. (2010). Severity and outcome of equine pasture-associated laminitis managed in first opinion practice in the UK. Veterinary Record, 167: 364-369. Orsini, J.A., Moate, P.J., Kuersten, K., Soma, L.R., & Boston, R.C. (2006). Pharmacokinetics of fentanyl delivered transdermally in healthy adult horses--variability among horses and its clinical implications. Journal of Veterinary Pharmacology and Therapeutics, 29: 539-546. Patterson-Kane, J.C., Karikoski, N.P., & McGowan, C.M. (2018). Paradigm shifts in understanding equine laminitis. The Veterinary Journal, 231: 33-40. Riggs, L.M., Krunkosky, T.M., Noschka, E., Boozer, L.A., Moore, J.N., Robertson, T.P., & Peroni, J.F. (2009). Comparison of characteristics and enzymatic products of leukocytes in the skin and laminar tissues of horses administered black walnut heartwood extract or lipopolysaccharide. American Journal of Veterinary Research, 70: 1383-1390. Stewart, A.J., Boothe, D.M., Cruz-Espindola, C., Mitchum, E.J., & Springfield, J. (2011). Pharmacokinetics of tramadol and metabolites O-desmethyltramadol and N-desmethyltramadol in adult horses. American Journal of Veterinary Research, 72: 967-974. Stewart, A.J., Pettigrew, A., Cochran, A.M., & Belknap, J.K. (2009). Indices of inflammation in the lung and liver in the early stages of the black walnut extract model of equine laminitis. Veterinary Immunology and Immunopathology, 129: 254-260. Stokes, S.M., Belknap, J.K., Engiles, J.B., Stefanovski, D., Bertin, F.R., Medina-Torres, C.E., Horn, R., & van Eps, A.W. (2019). Continuous digital hypothermia prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp model of equine laminitis. Equine Veterinary Journal, 51: 658-664. Terry, R.L., McDonnell, S.M., Van Eps, A.W., Soma, L.R., Liu, Y., Uboh, C.E., Moate, P.J., & Driessen, B. (2010). Pharmacokinetic profile and behavioral effects of gabapentin in the horse. Journal of Veterinary Pharmacology and Therapeutics, 33: 485-494. Thomasy, S.M., Slovis, N., Maxwell, L.K., & Kollias-Baker, C. (2004). Transdermal fentanyl combined with nonsteroidal anti-inflammatory drugs for analgesia in horses. Journal of Veterinary Internal Medicine, 18: 550-554. van Eps, A.W., Pollitt, C.C., Underwood, C., Medina-Torres, C.E., Goodwin, W.A., & Belknap, J.K. (2014). Continuous digital hypothermia initiated after the onset of lameness prevents lamellar failure in the oligofructose laminitis model. Equine Veterinary Journal, 46: 625-630. West, E., Bardell, D., Morgan, R., & Senior, M. (2011). Use of acetaminophen (paracetamol) as a short-term adjunctive analgesic in a laminitic pony. Veterinary Anaesthesia and Analgesia, 38: 521-522. Wylie, C.E., Newton, J.R., Bathe, A.P., & Payne, R.J. (2015). Prevalence of supporting limb laminitis in a UK equine practice and referral hospital setting between 2005 and 2013: implications for future epidemiological studies. Veterinary Record, 176: 72. 6 7Energy sources for performance horses Anouk Frieling, MSc Equine Sciences, BSc (Hons) energy requirements, the exercise level of an equine athlete Since domestication, the horse has developed into has to be taken into account when composing a diet. an incredible athlete being able to perform in diverse disciplines ranging from show jumping to endurance riding A horse performing high intensity exercise requires (Waller & Lindinger, 2010). Due to this development, the more energy in comparison to horses performing lower energy requirements of the horse have increased to enable intensity exercise (Table 1). Dietary energy can be derived it to perform optimally in each discipline (Harris, 1997). from various feedstuffs such as roughage and concentrates Energy is provided in the diet from fats, carbohydrates and in the UK is expressed in megajoules (Mj) of and protein, although the latter would only be a secondary digestible energy (DE). source. Dietary energy sources provide the body with fuel Table 1. Energy (Mj/DE per day) requirements depending on exercise to maintain normal biological functions such as growth and level based on a 500kg horse (NRC, 2007) repair. In performance horses there is also a large amount of Activity level Digestible energy (Mj/day) energy needed for muscle contraction (Treiber et al., 2008), Maintenance: no work 69.9 making energy a key consideration for performance horse Light exercise 83.7 diets. As the outdoor competition season has started, this Moderate exercise 97.5 article will explain the different types of energy sources that Heavy exercise 111.3 can be provided through the diet and how these different Very heavy exercise 144.3 sources support optimal performance for different types of exercise. Dietary fats are commonly supplemented to the diet DIETARY ENERGY SOURCES due to their ability to support and improve coat quality Energy is required for body maintenance, work, growth and shine. Besides their supportive function, fats are and reproduction (breeding, lactation) (Figure 1). For also energy dense nutrients which can be fed alongside the performance horse it is important to have good body carbohydrates to meet the increased energy requirement of condition as they should not be carrying excess weight the athletic horse (Warren & Vineyard, 2013). Fats are long- but should have energy stored in the body that can be used term energy sources, even though they are digested and absorbed fairly quick in the small intestine, fat metabolism during exercise (Nielsen, 2013). Therefore, to estimate Figure 1. Dietary energy is required for body maintenance, performing exercise, growth of the young horse and for reproduction. The daily energy requirement of the individual horse depends on the intensity of these four factors. 8 9Destrez et al., 2015). High-starch feedstuffs however do in the body is rather slow and therefore energy is slowly released from fats. Because fats are long-term energy provide sources of quick release energy, giving them a role sources they can deliver energy during exercise (Potter & in the diet if fed at appropriate levels. Gibbs, 2011) specifically during low-to moderate intensity Non-structural carbohydrates are mainly derived from exercise (Warren & Vineyard, 2013). Dietary fats can be concentrates and fresh grass in the form of starch and included by feeding plant-based oils such as linseed oil or sugars (Longland & Byrd, 2006). In the body starch and algae derived oils. sugars are transferred into glucose, a quickly accessible Carbohydrates can be divided into structural and non- form of energy ready for immediate use by the body. Excess structural carbohydrates. Structural-carbohydrates, also glucose is stored in muscle tissue in the form of glycogen known as fibre, are utilised in the horses body through which is able to provide energy in case blood glucose levels microbial fermentation in the hindgut into the volatile decrease (Potter & Gibbs, 2011). fatty acids (VFA’s) acetate, propionate and butyrate (Richardson & Murray, 2016). Fermentation of fibre, from Protein is a key nutrient for muscle development and roughage like hay, in the hindgut provides enough energy growth of the horse. Approximately 10-15% of the total to cover the energy requirements for horses performing body mass of the horse consists of protein with the muscles no or low-intensity exercise (Harris et al., 2017), however containing the largest part of the total percentage (Urschel & RE supplementation of fats and non-structural carbohydrates, P Lawrence, 2013). Dietary protein, which is mainly derived AP in the form of concentrates, is often required for horses from forages and concentrates, consist of amino acids that DE performing moderate or high-intensity exercise to meet L are necessary for protein synthesis in the body (Urschel & C their energy requirements (Jose-Cunilleras et al., 2002). Y Lawrence, 2013). Protein can be used as an energy source CE The feeding of high-starch diets often receives bad press as R by the body but this only happens if the diet does not contain % previous research analysing a high-fibre and high-starch diet 00 enough carbohydrates and fats to fulfil energy requirements 1 concluded that fibre supports the microbial composition in N (Johnson & Duberstein, 2010). Previously it was assumed the hindgut, digestive health and efficiency, whereas high- O D that excess protein was used as an energy source but more starch diets can cause ulcers (Andrews et al., 2017), and ET recent research explained that excess protein is excreted in also alter the microbial population and composition which NIRP the form of urea in urine. Therefore, this article will focus can result in colic or behavioural changes (Durham, 2009; Figure 2. Nutrient pools after absorption used for energy production in the body. 8 9on carbohydrates and fats as energy sources (Figure 2). ENERGY METABOLISM FED AND FASTED STATE Once carbohydrates and fats are digested and absorbed by the body the mitochondria, organelles in body cells, start to produce energy-carrying molecules (Bertram et al., 2006), of which adenosine triphosphate (ATP) is the main energy molecule in the body (Jonckheere et al., 2012). Energy in the form of ATP is either used immediately, which is called the fed state, or converted for storage by Figure 4. Once carbohydrates are digested into glucose they can either be used for energy production or stored in body cells. If glucose could be the body (Aird et al., 2018). When nutrients are no longer divided into cups, one cup would be used for energy production. When this cup is full another cup would be used for storage of glycogen. If available in the blood stream during intense exercise the after glycogen storage there is still excess glucose in the blood stream, body enters the fasted state and requires energy from then glucose would be converted into fatty acids which are stored in adipose tissue. the stored nutrients in body cells (Aird et al., 2018). The primary source for energy synthesis in cells is glucose oxygen to produce energy (Longo et al., 2016), of fatty acids + (Figure 3) (Bonora et al., 2012), mainly derived from and FADH2 creates the high energy molecules NADH + H dietary carbohydrates (Nafikov & Beitz, 2007). Besides which are used for ATP production (Turner et al., 2014). glucose, oxidation of fatty acids also produces ATP (Figure Full oxidation of fatty acids produces larger amounts of 3) (Turner et al., 2014). Oxidation, the process that requires ATP molecules in comparison to that of glucose, although this process requires greater amounts of oxygen. As such, fatty acids produce more energy than carbohydrates but require more oxygen per mole of ATP produced (Turner et al., 2014). Nutrients that are not immediately used for ATP production are stored in body cells and are used once the horse performs heavy exercise (Harris & Schott, 2013). Excess fatty acids are converted into triglycerides through the process of lipogenesis which mainly occurs in adipose tissue but can also occur in the liver, heart, muscles and pancreas (Saponaro et al., 2015). Excess glucose is converted into glycogen, a glucose polymer (Adeva- Andany et al., 2016), and stored in liver and muscle cells through the process of glycogenesis which is generated by the release of the hormone insulin by the pancreas (Rui, 2014). If there is still excess glucose after energy synthesis and storage in the form of glycogen, glucose is transferred into fatty acids through de novo lipogenesis (Schutz, 2004), and can therefore be stored in adipose tissue (Figure 4) (Ameer et al., 2014). Glycogen and triglycerides are converted into glucose Figure 3. The three processes involved with ATP synthesis. The first and fatty acids once the horse proceeds into the fasted state process is transferring glucose from the diet into pyruvate which reacts with coenzyme A before entering the TCA cycle. The TCA cycle produces during exercise and requires energy from stored nutrients high energy electrons which are involved with the high quantity of ATP as they cannot eat to produce energy (Figure 5) (Polak (Silverthorn, 2015). 10 11Figure 5. Metabolic processes utilising dietary energy sources and energy stored within the body to provide muscles with energy during exercise. are met (Harris & Schott, 2013). Opposed to endurance et al., 2008; Han et al., 2016). Glycogen is converted through glycogenolysis, a process that does not necessarily horses, race horses perform intense exercise within shorter require oxygen and therefore glucose can be released periods and require a combination of quick and slow quickly during intense muscular activity when oxygen releasing energy to deliver energy for muscle contraction is scarce (Müller et al., 2012). Although the anaerobic during this form of exercise (Nielsen, 2013). Therefore, a metabolism (metabolism without oxygen) of glucose can diet based on roughage supplemented with non-structural REP be useful during exercise, the process also creates lactic carbohydrates, will be able to supply this type of energy AP acid and yields less ATP compared to aerobic metabolism release. To meet the energy requirements and maintain DE (metabolism with oxygen) of fatty acids and glucose body condition, without feeding excessive amounts of LCY (Harris & Schott, 2013). Trough the lipolysis process starch, fats can be supplemented to the diet (Nielsen, 2013). CE triglycerides are converted into fatty acids (Richard et al., R Overfeeding carbohydrates or fats can results in % 2000). Fatty acids are always metabolised through aerobic 0 constantly triggering the pancreas to release insulin (Wilcox, 01 mechanisms, therefore lipolysis requires oxygen which 2005; Warren & Vineyard, 2013). This constant release can NO results in a slower release of fatty acids in the blood stream, result in insulin insensitivity or resistance, meaning that the DE in comparison to glucose, during intense exercise, making T cells do not respond properly to the release of insulin and NI it a long-term energy source (Harris & Schott, 2013). R are unable to store all the excess glucose circulating in the P blood stream (Kaczmarek et al., 2016). Insulin resistance FEEDING THE EQUINE ATHLETE is associated with health issues such as Equine Metabolic As previously discussed carbohydrates and fats are Syndrome (EMS) and laminitis. For more information metabolised through different pathways which creates either about insulin resistance and EMS, please refer to Equine short-term or long-term energy supplies for the horse. Due metabolic syndrome, or for further information on laminitis to the difference in either short or long-term energy supply see Update on laminitis. the discipline in which the equine athlete performs should be taken into account when formulating a diet. Endurance Due to the quick or slow energy release of fats and horses for example require slow releasing energy sources, carbohydrates, the feeding time before exercise should which can be provided through dietary fats and a high-fibre also be taken into account as energy needs to be available diet, as endurance horses exercise for prolonged periods when the muscles require it during exercise. Previously (Harris & Schott, 2013). Roughage, a fibrous feedstuff, Pagan & Harris (1999) explained that feeding grain should is also able to retain fluids and electrolytes which are be avoided prior to exercise as it was shown to affect especially important during prolonged exercise such as glycaemic response and reduced the availability of fatty endurance (Harris, 2009). Non-structural carbohydrates in acids. Because of this response, fatigue occurs earlier when the form of concentrates can be supplemented to maintain horses are exercised shortly after consuming concentrates body weight and to make sure other nutrients requirements (Harris & Harris, 2005). Brunner et al. (2015) found that 10 11immediately used by the body for example for maintenance feeding roughage 2-4 hours prior to exercise to show or light exercise but excess energy can also be stored in jumping horses had a positive significant effect on the liver cells, muscle cells or adipose tissue. By storing excess blood parameters glucose, lactate, insulin, triglycerides and energy, the body can provide its own energy if the horse free fatty acids, whilst concentrate feeding did not have is exercising intensively and is not able to consume feed. a significant effect. Therefore, research has shown that Energy sources are either released quickly or slow and feeding time and energy source are important to consider therefore the discipline of the horse should be taken into so that the horse is able to perform optimally. account when composing a diet as performing in different disciplines require different types of energy. Besides the SUMMARY type of energy source, the feeding time also has an effect on For the performance horse the energy sources in the diet the energy availability during exercise and should therefore are carbohydrates and fats. These nutrients can be included also be taken into account. Therefore, for the athletic in the diet by providing the horse fibrous feeds like hay, performance horse it is important that the diet contains concentrates or plant-based oils like linseed oil. Once these enough energy to maintain body condition and is adjusted nutrients are digested and absorbed by the body, they will to the workload and discipline to provide energy that is undergo metabolic processes that will convert them into required during exercise. ATP which is an energy carrying molecule. Energy can be REFERENCES Adeva-Andany, M. M., González-Lucán, M., Donapetry-García, C., Fernández-Fernández, C., & Ameneiros-Rodríguez, E. (2016). Glycogen metabolism in humans. BBA Clinical, 5: 85-100. Aird, T. P., Davies, R. W., & Carson, B. P. (2018). Effects of fasted vs fed-state exercise on performance and post-exercise metabolism: A systematic review and meta-analysis. Scandinavian Journal of Medicine and Science in Sports, 28(5): 1476-1493. Ameer, F., Scandiuzzi, L., Hasnain, S., Kalbacher, H., & Zaidi, N. (2014). De novo lipogenesis in health and disease. Metabolism: Clinical and Experimental, 63(7): 895-902. Andrews, F. M., Larson, C., & Harris, P. (2017). Nutritional management of gastric ulceration. Equine Veterinary Education, 29(1): 45-55. Bertram, R., Gram Pedersen, M., Luciani, D. S., & Sherman, A. (2006). A simplified model for mitochondrial ATP production. Journal of Theoretical Biology, 243(4): 575-586. Bonora, M., Patergnani, S., Rimessi, A., de Marchi, E., Suski, J. M., Bononi, A., Giorgi, C., Marchi, S., Missiroli, S., Poletti, F., Wieckowski, M. R., & Pinton, P. (2012). ATP synthesis and storage. Purinergic Signalling, 8(3): 343-357. Brunner, J., Liesegang, A., Weiss, S., & Wichert, B. (2015). Feeding practice and influence on selected blood parameters in show jumping horses competing in Switzerland. Journal of Animal Physiology and Animal Nutrition, 99(4): 684-691. Destrez, A., Grimm, P., Cézilly, F., & Julliand, V. (2015). Changes of the hindgut microbiota due to high-starch diet can be associated with behavioral stress response in horses. Physiology and Behavior, 149: 159-164. Durham, A. E. (2009). The Role of Nutrition in Colic. Veterinary Clinics of North America - Equine Practice, 25(1): 67-78. Han, H. S., Kang, G., Kim, J. S., Choi, B. H., & Koo, S. H. (2016). Regulation of glucose metabolism from a liver-centric perspective. Experimental and Molecular Medicine, 48(3): 1-10. Harris, P. (1997). Energy sources and requirements of the exercising horse. Annual Review of Nutrition, 17: 185-210. Harris, P. A., Ellis, A. D., Fradinho, M. J., Jansson, A., Julliand, V., Luthersson, N., Santos, A. S., & Vervuert, I. (2017). Review: Feeding conserved forage to horses: recent advances and recommendations. Animal, 11(6): 958-967. Harris, P. A., & Harris, R. C. (2005). Ergogenic potential of nutritional strategies and substances in the horse. Livestock Production Science, 92(2): 147-165. Harris, P. (2009). Feeding Management of Elite Endurance Horses. Veterinary Clinics of North America - Equine Practice, 25(1): 137-153. Harris, P. A., & Schott, H. C. (2013). Chapter 14 - Nutritional management of elite endurance horses. In: Geor, R.J., Harris, P.A., & Coenen, M., (Eds.). Equine Applied and Clinical Nutrition. Saunders Elsevier: China. Johnson, E. L., & Duberstein, K. J. (2010). How to Feed a Horse : Understanding Basic Principles of Horse Nutrition. University of Florida, IFAS Extension, 2010(2): 1-5. Jonckheere, A. I., Smeitink, J. A. M., & Rodenburg, R. J. T. (2012). Mitochondrial ATP synthase: Architecture, function and pathology. Journal of Inherited Metabolic Disease, 35(2): 211-225. Jose-Cunilleras, E., Hinchcliff, K. W., Sams, R. A., Devorand, S. T., & Linderman, J. K. (2002). Glycemic index of a meal fed before exercise alters substrate use and glucose flux in exercising horses. Journal of Applied Physiology, 92(1): 117-128. Kaczmarek, K., Janicki, B., & Głowska, M. (2016). Insulin resistance in the horse: A review. Journal of Applied Animal Research, 44(1): 424-430. Longland, A. C., & Byrd, B. M. (2006). Pasture nonstructural carbohydrates and equine laminitis. Journal of Nutrition, 136(7): 2099-2102. Longo, N., Frigeni, M., & Pasquali, M. (2016). Carnitine transport and fatty acid oxidation. Biochimica et Biophysica Acta - Molecular Cell Research, 1863(10): 2422-2435. Müller, M., Mentel, M., van Hellemond, J. J., Henze, K., Woehle, C., Gould, S. B., Yu, R.-Y., van der Giezen, M., Tielens, A. G. M., & Martin, W. F. (2012). Biochemistry and Evolution of Anaerobic Energy Metabolism in Eukaryotes. Microbiology and Molecular Biology Reviews, 76(2): 444-495. Nafikov, R. A., & Beitz, D. C. (2007). Carbohydrate and lipid metabolism in farm animals. Journal of Nutrition, 137(3): 702-705. Nielsen, B. D. (2013). Chapter 13 - Practical considerations for feeding racehorses. In: Geor, R.J., Harris, P.A., & Coenen, M., (Eds.). Equine Applied and Clinical Nutrition. Saunders Elsevier: China. NRC. (2007). Nutrient Requirements of Horses, Nutrient Requirements of Horses. Pagan, J. D., & Harris, P. A. (1999). The effects of timing and amount of forage and grain on exercise response in thoroughbred horses. Equine Veterinary Journal, 30: 451-457. Polak, J., Bajzova, M., & Stich, V. (2008). Effect of exercise on lipolysis in adipose tissue. Future Lipidology, 3(5): 557-572. Potter, G. D. & Gibbs, P. G. (2011) Feeding the Performance Horse. Texas a & M University Department of Animal Science Equine Sciences Program. Richard, A. J., White, U., Elks, C. M., & Stephens, J. M. (2000). Adipose Tissue: Physiology to Metabolic Dysfunction. Endotext. Richardson, K., & Murray, J. A. M. D. (2016). Fiber for Performance Horses: A Review. Journal of Equine Veterinary Science, 46: 31-39. Rui, L. (2014). Energy metabolism in the liver. Comprehensive Physiology, 4(1): 177-197. Saponaro, C., Gaggini, M., Carli, F., & Gastaldelli, A. (2015). The subtle balance between lipolysis and lipogenesis: A critical point in metabolic homeostasis. Nutrients, 7(11): 9453-9474. Schutz, Y. (2004). Dietary fat, lipogenesis and energy balance. Physiology and Behavior, 83(4): 557-564. Shimazu, T. (1981). Central nervous system regulation of liver and adipose tissue metabolism. Diabetologia, 20(1): 343-356. Silverthorn, D. U. (2015). Human Physiology: An Integrated Approach, Global 7th Edition. Pearson, Londen, UK. Treiber, K. H., Geor, R. J., Boston, R. C., Hess, T. M., Harris, P. A., & Kronfeld, D. S. (2008). Dietary energy source affects glucose kinetics in trained arabian geldings at rest and during endurance exercise. Journal of Nutrition, 138(5): 964-970. Turner, N., Cooney, G. J., Kraegen, E. W., & Bruce, C. R. (2014). Fatty acid metabolism, energy expenditure and insulin resistance in muscle. Journal of Endocrinology, 220(2): 61-79. Urschel, K. L., & Lawrence, L. M. (2013). Chapter - 6 Amino acids and protein. In: Geor, R.J., Harris, P.A., & Coenen, M., (Eds.). Equine Applied and Clinical Nutrition. Saunders Elsevier: China. Waller, A. P., & Lindinger, M. I. (2010). Nutritional aspects of post exercise skeletal muscle glycogen synthesis in horses: A comparative review. Equine Veterinary Journal, 42(3): 274-281. Warren, L. K., & Vineyard, K. R. (2013). Chapter - 7 Fat and fatty acids. In: Geor, R.J., Harris, P.A., & Coenen, M., (Eds.). Equine Applied and Clinical Nutrition. Saunders Elsevier: China. Wilcox, G. (2005). Insulin and Insulin Resistance Gisela. Alimentary Pharmacology and Therapeutics, Supplement, 22(2): 63-82. 12 13Liver disease in horses Eduardo Alguacil, MRCVS, Uplands Way Veterinary Practices develop liver disease (West,1996). The only way to identify The liver is the largest organ in the body of the horse. liver disease is with the clinical signs, as the liver cannot be It is in charge of metabolising carbohydrates, proteins, and seen, heard, or palpated. When they start to show clinical fat and can also excrete numerous toxic compounds. It can signs, the damage could be irreversible. Early clinical perform different functions, including endocrine (secretes signs could be unspecific such as weight loss, anorexia, hormones/products directly into the blood) and exocrine lethargy, abdominal pain (colic) and jaundice (Figure 1). (secretes hormones/products through a duct) functions. Other clinical signs could be stridor (abnormal respiratory Most of the nutrients absorbed from the gastrointestinal noise), photosensitisation (skin changes due to ultraviolet tract pass via portal circulation straight to the liver, where sunlight) or diarrhoea. In severe or advanced cases, the they are metabolised. They are then repackaged, stored, or horse can develop hepatic encephalopathy (developing exported to peripheral tissues. RE neurologic problems). PA Humans and horses can survive with a liver that is P When the horse develops icterus (yellowing of the skin, D Tail not 100% healthy as this organ can regenerate itself, so E gums, and whites of the eyes) this is due to the liver's LC it provides protection against permanent damage. Horses Y incapacity to take up, conjugate and excrete bilirubin. CE might survive with only 20% of a functioning liver, R Before this happens, we have some laboratory tests that % although when the damage is more than 80%, they can start 0 may detect disease before the failure. In these tests, we 01 to develop clinical signs (Durham et al., 2003). can see how some functions of the liver fail, giving a NO prognosis and a progression of the clinical signs (Parraga The liver in the horse is susceptible to developing DET et al., 1995). Routine biochemical tests, including hepatic disease as it works as a clearance organ for many toxins, NIR enzymes such as gamma-glutamyl transferase (GGT), and grazing animals like horses are more predisposed to P glutamate dehydrogenase (GLDH), alkaline phosphatase (ALP) and aspartate aminotransferase (AST), can tell us if liver disease is present. However, to assess liver function more accurately we need a more specific test to measure specific liver parameters such as bile acid and bilirubin concentrations. An additional blood test can give extra information like prolonged blood clotting times, hyperglobulinaemia and increased ammonia concentration, however the most accurate test for the diagnosis of liver disease is a liver biopsy. Taking a sample from the organ lets us know the causes and the severity of the liver disease. Other tests we can carry out are a hepatic ultrasound to check the hepatic size, the appearance of the liver, look for tumours or abscesses, and abdominal radiographics with Figure 1. Yellowing of the mucus membranes indicates jaundice, a contrast to determine if the liver presents any obstruction. symptom of liver damage. 12 13MAIN LIVER DISEASES: TOXICS Pyrrolizidine alkaloid (PA) poisoning: PA toxicity is commonly due to ingestion of Common Ragwort in the UK (Figure 2), but other plants also contain this toxin (Clarke et al., 1981; Caloni & Cortinovis, 2015). When the PA are ingested, the alkaloids are broken down to pyrrols in the liver. Although unpalatable, ragwort consumption occurs when poor pasture or hay grazing is contaminated (Vandenbroucke et al., 2010). Most horses with PA poisoning develop chronic and delayed clinical signs. The main clinical signs are weight loss, icterus and Figure 2. Ragwort (Senecio jacobaea) is a common cause of liver lethargy although horses and ponies may not become damage in horses. unwell until a year after ingestion of PAs, making such toxicity challenging to diagnose. The liver enzymes are Other Hepatotoxins: Many products can be toxic to altered before showing any other clinical signs. The serum the liver, including other plants, chemicals and drugs GGT, ALP and total bile acids concentrations are the most administered by your veterinarians. Indeed, clinical signs sensitive indicators of this chronic disease. and laboratory tests do not differentiate between the different toxins, but with the diagnosis of liver disease The animal starts to deteriorate, developing other and a good anamnesis the clinician can try to identify the symptoms such as respiratory disease due to bilateral specific toxin. laryngeal paralysis (Fu et al., 2002; Lahse et al., 2018). ACUTE HEPATITIS (THEILER’S DISEASE) Although the origin of this paralysis is unknown, it could be Acute hepatitis is developed suddenly in a short- related with hyperammonaemia as it can develop functional term, producing inflammation of the liver. The causes neuromuscular disorders (McGorum et al., 1999). of this disease are diverse, such as administration of Most cases cannot be treated once the clinical signs have tetanus antitoxin, infection (blood transfusions), poisons started, especially when we have found histopathological or undefined causes (Hjerpe, 1964). Most of the cases changes, the liver enzymes are altered, and the animal are developed in the summer season, and it may be that presents neurological signs. In early stages, before the horse a vector (intermediate carrier or transporter) is related as suffers changes in the liver, removing the feed containing some horses present acute hepatitis that have not been PAs, and supporting liver function, the horse might survive. administered any serum product but are exposed to horses Mycotoxins: These are naturally occurring toxic which have. Lactating mares that receive tetanus antitoxin substances which are produced by moulds and fungi in at foaling seem to be more susceptible. your horse’s forage (Penicillium and Aspergillus) or pasture The clinical signs appear between 4-10 weeks after (Fusarium and Endophyte toxins). The environmental exposure. Acute hepatitis can be sporadic, but in most conditions can lead to an increase in the levels of toxins cases, there are more animals involved. The clinical signs produced, with toxins able to be stored on the grass or are lethargy, icterus, and anorexia. The urine has a dark forage for a long time. There are a variety of clinical signs, colour because of the high bilirubin concentration. Weight such as liver disease, colic, hypersensitivity, abortions, and loss is not common as the signs are acute. Severe cases can develop hepatic encephalopathy. Death may occur neurological disorders. 14 15suddenly in 50% to 60% (with an overall death rate as high The aetiology is unknown, and multiple agents may be as 88%) of affected horses. involved. The clinical signs are multiple and not specific. Most of them are related with chronic liver diseases For diagnosis, it is necessary to perform a liver biopsy to such as depression, weight loss, and neurological signs. confirm, although, with the history, clinical signs and blood Fever could appear if a bacterial infection is the cause tests we can make an approach to the diagnosis. There is no of the disease, and icterus could be present, but it is not specific treatment for acute hepatitis, but your veterinarian mandatory. Some horses have moist exfoliative dermatitis can give some supportive therapy. at the coronary bands due to vasculitis. It is difficult CHOLANGIOHEPATITIS clinically to differentiate these horses from those with PA Cholangiohepatitis is severe inflammation of the bile toxicity. For a diagnosis, a liver biopsy is necessary and ductus and adjacent liver, and it can lead occasionally should demonstrate ongoing but chronic hepatitis. to liver failure in horses. This disease appears as a Many horses with chronic active hepatitis that is detected consequence of an intestinal infection migrating to the liver early before bridging fibrosis occurs can be saved. We (most of the cases by Salmonella spp.) or parasite infection need to make an accurate diagnosis to provide appropriate such as flukes (Figure 3). It has also been associated with treatment, as in cases where the main cause of the disease stones in the bile duct, intestinal inflammation, tumours R is bacterial infection, antibiotics should be used, but when and some toxins. EP it is just related with inflammation, corticosteroids can AP be used. DELC HYPERTRIGLYCERIDAEMIA, HEPATIC LIPIDOSIS YCE Hypertriglyceridemia is defined as an increase in plasma R % triglyceride concentration, without the animal presenting 001 associated clinical symptoms (Dunkel & McKenzie, 2003). NO It usually occurs as a complication more frequently in ill DE animals or those with high energy demands (pregnant or TNI lactating mares), in sick animals with secondary insulin RP resistance, for example, a systemic inflammatory response syndrome (SIRS), in animals that cannot ingest food Figure 3. Grazing horses with sheep can lead to liver fluke infection. (chewing problems, dysphagia, prolonged fasting) or in genetically predisposed sick animals such as ponies The clinical signs could be more related with colon and donkeys. In these cases, it may be primary. The damage, but liver enzymes are increased, and bilirubin and most characteristic clinical signs are apathy, anorexia, total bile acid concentrations may be disproportionately depression, weight loss, hyperthermia and in more severe high. For diagnosis we can evaluate with ultrasound the cases, can lead to fatty infiltration of the liver and liver length of the ductus, checking if it is larger than normal, failure (Mackenzie, 2011). and then a liver biopsy is necessary to obtain a sample of tissue to perform a culture. For the treatment, we can use Diagnosis is based on finding white-to-yellow opacity antibiotics as they are excreted in the bile. of the serum caused by the high lipid content. Cholesterol is also increased, indicating an increase in lipoprotein. CHRONIC ACTIVE HEPATITIS Treatment to control hypertriglyceridaemia focuses on This disease is a chronic inflammation in the liver. It is reversing the catabolic state in which the animal is in to well described in humans and dogs. The inflammation is stop the mobilisation of triglycerides from adipose tissue. localised in the periportal area (Carlson & Vivrette, 1989). 14 15Eduardo Alguacil, MRCVS, Uplands Way Veterinary Practices Eduardo joined Uplands Way three years ago having qualified from University of Cordoba, Spain in 2014, and specialises in internal medicine cases and dentistry. Having decided that he wanted to focus on horses he spent a few months working in Ireland before completing an equine internship at the equine hospital of the University of Barcelona. Before moving to the UK, Eduardo worked at an endurance stud with the foals, and has a keen interest in endurance riding having competed in races in Spain. TREATMENT OF LIVER DISEASE IN THE HORSE levels up. The proteins should be limited, but need to be of The success of treatment in liver disease is better when high quality, so the amino acids are not used for energy which the disease is in the early stages or acute phases. As the increases the amount of ammonia produced. Excess protein liver has a good capacity to regenerate when we treat it may lead to hyperammonemia and hepatic encephalopathy, in early stages, the outcome is usually good. The first aim but some protein is needed for regeneration of the liver and of the treatment has to be to eliminate the main cause. to produce lipoprotein to mobilise fat from the liver. Diets Sometimes when it is in advanced phases, only eliminating with a high amount of amino acids could improve the grade the main cause is not enough to recover the liver of hepatic encephalopathy. Vitamin E and Selenium have function completely. also been demonstrated to be beneficial for this pathology. When the veterinarian is going to use any drugs, they Prevention of liver disease is the most important need to think about where the drug is metabolised, as it can treatment. Reducing exposure of the animal to hepatotoxic affect the liver function. One of the most important points plants, herbicide sprays, removing the horse from pastures in the treatment of liver disease is diet management. It is with sheep, or using biological control such as the cinnabar essential to control the calorie intake. Feeds with readily digestible carbohydrates may help keep the blood glucose moth, is the best therapy to avoid equine liver disease. REFERENCES Caloni, F., & Cortinovis, C. (2015). Plants poisonous to horses in Europe! Equine Veterinary Education, 27(5): 269-274. Carlson, G.P., & Vivrette, S. (1989). Chronic active hepatitis in horses. In: Proceedings of the American College of Veterinary Internal Medicine Forum 7: 595. Clarke, M., Harvey, D., & Humphreys, D. (1981). Veterinary Toxicology, 2nd ed., Bailliere Tindall: London: 203-206. Dunkel, B., & McKenzie, H.C. (2003). Severe hypertiglyceridaemia in clinically ill horses: diagnosis, treatment and outcome. Equine Veterinary Journal, 35(6): 590-595. Durham, A. E., Smith, K. C., Newton, J. R., Hillyer, M. H., Hillyer, L. L., Smith, M. R., & Marr, C. M. (2003). Development and application of a scoring system for prognostic evaluation of equine liver biopsies. Equine Veterinary Journal, 35(6): 534–540. Fu, P., Xia, Q., Lin, G., & Chou, M. (2002). Genotoxic pyrrolizidine alkaloids - mechanisms leading to DNA addict formation and tumorigenicity. International Journal of Molecular Sciences, 3: 948-964. Mackenzie, H,C. (2011). Equine Hyperlipidemias. Veterinary Clinics of North America: Equine Practice, 27: 59-72. Hjerpe, C.A. (1964). Serum hepatitis in the horse. Journal of American Veterinary Medical Association, 144: 734-74. Lahse, J., Paredes, E., Gonzalez, C., Koene, M., & Mageed, M. (2018). Pyrrolizidine alkaloid toxicosis and hepatic encephalopathy in horses in Easter Island, Chile. Australian Journal of Veterinary Science, 50:107-110. McGorum, B., Murphy, D., Love, S., & Milne, E. (1999). Clinicopathological features of equine primary hepatic disease: a review of 50 cases. Veterinary Record, 145: 134-139. Parraga, M.E., Carlson, G.P., & Thurmond, M. (1995). Serum protein concentrations in horses with severe liver disease: a retrospective study and review of the literature. Journal of Veterinary Internal Medicine, 9: 154-161. Tennant, B. (1978). Acute hepatitis in horses: problems of differentiating toxic and infectious causes in the adult. Proceedings of the American Association of Equine Practitioners, 24: 465-471. Vandenbroucke, V., Van Pelt, H., De Backer, P., & Croubels, S. (2010). Animal poisonings in Belgium: a review of the past decade. Vlaams Diergeneeskundig Tijdschrift, 79: 259-268. West, H. J. (1996). Clinical and pathological studies in horses with hepatic disease. Equine Veterinary Journal, 28: 146–156. 16 17Equine plant toxicity: toxic metabolites, internal systems affected and management Rebecca Allan, Equine Nutritionist Approaching the height of summer and increased daylight hours means plants can absorb more energy from sunlight to grow (Jou et al., 2015). Although full-bloom paddocks and gardens are beautiful to see, some plants can have detrimental effects on your horse’s health and wellbeing. All plants have secondary compounds some of which are toxic to animals if consumed in sufficient quantities (James et al., 2005). Equids are monogastric animals making them more susceptible and less able to tolerate toxins than ruminants Figure 1. Equine physiology and grazing habitats make them perfect (Loh et al., 2020). Their physiology combined with their R candidates for plant intoxication. E grazing habits of constantly looking for new food material PAP substances present in plants fall under the category of and having strong incisors that enable them to eat plants DE secondary metabolites as they act as a defence mechanism down to the soil, even eating root material (Webster, 2013), LC (Copper & Johnson, 1998). Y make equids the perfect candidate to become intoxicated CE by plant sources (Figure 1). Veterinary Investigation R Poisonous plants can be classed biochemically according % Centres in Britain showed that 15-17% of poisoning cases 0 to their toxic principles, so whether the toxins have been 01 in animals were due to plants, showing just how much of synthesised within the plant or selectively concentrated N a threat equids are exposed to (Copper & Johnson, 1998). O from the soil (Copper & Johnson, 1998). The toxins D The plants are the causative agents although it is the toxic E which possess a greater threat to equines are grouped into TN dosage, and the equine internal systems affected, that I alkaloids, cyanogenic and cardiac glycosides, tannins, and RP influence the severity of the intoxication. photodynamic substances (Hastie, 2012). The following is a description of these toxins linked to the common poisonous PLANT TOXINS plants in the UK which can be seen in Table 1. Appendix 1 The toxic effects that equids experience when ingesting provides a visual guide to these common plants. poisonous plants are due to specific toxic compounds ALKALOIDS present within the plant. Metabolites are known as the substances produced by the plant which can be subdivided Alkaloids are nitrogen-containing secondary metabolites into primary and secondary (Pavarini et al., 2012). The with approximately 20% of plant species containing them, primary metabolites are those essential to the plant’s in fact, alkaloids are more likely to poison livestock than growth and development, whilst secondary metabolites any other toxic compound (Pfister et al., 2001; Heinrich et are naturally occurring compounds, functioning as al., 2021) From a biochemical perspective, alkaloids consist defensive agents, the synthesis of which is influenced by of a heterocyclic ring with a nitrogen atom acting as a base, the environment and predators around the plant (Copper however, this arrangement in structure can vary leading & Johnson, 1998; Pavarini et al., 2012). Through studying to subtype groups such as piperidine and pyrrolizidine plant biology, it is thought secondary metabolites are a alkaloids amongst others (Copper & Johnson, 1998). plant's way to communicate and respond to external stimuli Alkaloids are commonly associated with liver damage, (Pavarini et al., 2012). It is for this reason the poisonous 16 17central nervous system defects and weight loss, followed stage of this plant to be the most toxic (Zentek et al.,1999). by hepatic encephalopathy in extreme cases which are later Ragwort (Senecio species) is composed of more than described (Mair & Love, 2012; Hall et al., 2020). 1200 species worldwide with 25 species confirmed poisonous (Anadón et al., 2012). These plants contain a PIPERIDINE CONTAINING ALKALOIDS series of PA such as senecioninie, jacidine and jacozine Poison Hemlock (Conium maculatum) contains several amongst others. In the UK and Belgium, there have piperidine alkaloids which are prevalent within the been many reported incidents involving the exposure plant and probably responsible for its toxicity (Copper of horses to Tansy Ragwort (Crews & Anderson, 2009; & Johnson, 1998). The concentrations at which these Vandenbroucke et al., 2010). alkaloids are present vary with the stage of plant growth and environmental conditions (Matsuura & Fett-Neto, 2015). OTHER ALKALOIDS The leaves are dangerous in the spring whereas the fruit is European Yew (Taxus baccota) is composed of volatile very dangerous in the autumn (Anadón et al., 2012). Poison oils in the tree sap acting as irritants together with a Hemlock is often confused with the extremely poisonous complex mixture of taxine alkaloids (Anadón et al., 2012). Water Hemlock, the main characteristic distinguishing them The taxine is present throughout the Yew but not in the is that the Water Hemlock has visually distinct partitions in red fruit (Anadón et al., 2012). European Yew poisoning the roots (Panter et al., 2012). in horses can also occur from ingestion of Yew clippings Marsh Horsetail (Equisetum palustre) is a non- (Berny et al., 2010). flowering, fern-like poisonous plant which contains several Nightshade plant species (Solanum species) can also compounds leading to its toxic nature. Alongside piperidine induce toxicity in equines. The Solanum toxins vary from alkaloids, it also contains a nicotine alkaloid and thiaminase species, although solanine is the common glycoalkaloid enzyme (Copper & Johnson, 1998; Cramer et al., 2015). across all nightshade species (Norman et al., 2012). Within Interestingly, a recent study on cattle revealed that Marsh the UK, Deadly Nightshade and Woody Nightshade are Horsetail is a major source of piperidine alkaloids, and it is the nightshade variants containing glycoalkaloids affecting the reason why cattle are exposed to this compound (van horses (Copper & Johnson, 1998; Hastie, 2012). Raamsdonk et al., 2015). Horses are reported among the GLYCOSIDES sensitive species to Marsh Horsetail, showing disturbance to their balance if consumed (Cramer et al., 2015). The term glycoside involves a large group of organic substances which are composed of one or more PYRROLIZIDINE CONTAINING ALKALOIDS monosaccharide (sugar) molecules combined with a non- Pyrrolizidine alkaloids (PA) are specifically synthesised sugar entity, known as aglycone (Copper & Johnson, in the root of plants and then translocated to all other plant 1998). Although many plants containing glycosides are organs (Ober & Hartmann, 1999). not toxic, their toxicity is determined by the aglycone and Hound´s Tongue (Cynoglossum officinale) invades the properties of the latter enable sub-classification into pastures and fields, although it is mostly unpalatable cyanogenic, goitrogenic, cardiac and saponic glycosides, to horses therefore most intoxication occurs when hay although not every toxin fits into these groups (Copper & or forage is contaminated (Copper & Johnson, 1998; Johnson, 1998). Stegelmeier, 2011). It contains four pyrrolidine alkaloids: Buttercups (Ranunculus repens) contain the glycoside 7-angelyheliotridine, echinatine, acetylheliosupine and ranunculin with the aglycone protoanemonin being the heliosupine, with the latter being 4-6 times more toxic toxic agent which is of a strong oil nature (Majak, 2001; (Pfister et al., 1992). In Europe there was an accident report, Dalefield, 2017). This is an example of a glycoside whereby Hound´s Tongue was indicated as a potential toxic containing plant that has not been classified into a category threat to horses in pasture, specifying the early growth (Copper & Johnson, 1998). 18 19photosensitivity: St John´s Wort (Hypericum perforatum) CARDIAC GLYCOSIDES and Buckwheat (Fagopyrum esculentum). St John´s Wort Foxglove (Digitalis purpurea) is a highly toxic plant contains hypericin as the photosensitiser agent, whilst that contains cardiac glycosides. These glycosides have a Buckwheat contains the pigment Fagopyrin as the active specific action on the heart, increasing the contractility of principle (Copper & Johnson, 1998; Hastie, 2012). the heart, and slowing down the heart rate. In Foxglove, the toxic agent is termed Digitalis glycosides (also known as BODY SYSTEMS AND ORGANS DAMAGED BY Digoxin) (Copper & Johnson, 1998; Kurian, 2015). PLANT TOXINS CYANOGENIC GLYCOSIDE Every equine is an individual and their susceptibility Bracken Fern (Pteridium aquilinum) has several harmful to individual poisonous plants will vary. Symptoms constituents. The main concerns that have been identified resulting from the consumption of toxic plants happen at are cyanogenic glycoside (prunasin) which is often present various speeds and intensities, creating a challenge for in harmless quantities, together with the enzyme thiaminase both vets and horse owners (Hastie; 2012). Some horses and a carcinogen (ptaquiloside) (Copper & Johnson, consume toxic plants and only become mildly ill whilst 1998). The effects of thiaminase are the primary cause of others become severely ill. It is the type of toxin consumed toxicity in equids as they can cause vitamin B1 deficiency. and its quantity that will determine the clinical signs, Although prunasin content in bracken is usually too low although they are usually multifactorial (Hastie, 2012). RE to harm animals, the prunasin glycoside metabolises into P Furthermore, some toxic compounds affect vital organs A hydrocyanic acid as the plants are crushed during eating, P without any symptomatic warning until the organ is mostly D and death has been reported from animals eating young E compromised, as is the case for liver disease (Mair & LC bracken leaves (Copper & Johnson, 1998). Y Love, 2012). CE TANNINS R The foremost indicator of a toxic event is any meaningful %0 change in your horse’s behaviour. Any inconsistency or Tannins are complex phenolic polymers that vary in 01 uncommon behaviour should be a cause for concern (Sestric biological activity and chemical structure. The Oak tree, NO & Coates-Markel, 2005; Hastie, 2012). The more common including the acorns and leaves, contains tannins and is a DE signs are change in appetite, observable physical trauma, common cause of tanning poisoning in the UK (Copper & TNI digestive changes/upsets, neurological symptoms together Johnson, 1998). When consumed by horses, the tannins can RP with muscle loss and weakness (Hastie, 2012; Stegelmeier be broken down by bacteria in the gastrointestinal tract and & Davis, 2018). The variability in clinical signs is due to can give rise to gastroenteritis (Copper & Johnson, 1998; the different body systems affected, with some toxins more Hastie, 2012). prevalently affecting certain body systems. PHOTODYNAMIC SUBSTANCES Equine toxicity progresses as follows: the Photodynamic substances can make non-pigmented gastrointestinal, cardiovascular, and nervous systems or slightly pigmented skin hypersensitive or hyper- are primarily affected and then as toxin ingestion has reactive to ultraviolet radiation in sunlight (Hastie, 2012). developed, further secondary changes can be seen from Photodynamic substances become toxic when exposed to hepatic (liver) failure and encephalic (brain and nerves) light due to their chemical properties, meaning they absorb systems (Hastie, 2012). Following on, the physiology of light wavelengths within the ultraviolet (UV) and visible how the bodily systems are affected by toxins is described. spectrum (280-700nm) (Collett, 2019). For a compound to be an effective photo toxin it should be absorbed through GASTROINTESTINAL SYSTEM the gastrointestinal tract or through direct skin contact in Once a potentially toxic compound is ingested, the sufficient concentrations (Copper & Johnson, 1998). initial interaction and damage occur in the gastrointestinal enterocytes (absorption cells lining the intestines), affecting In the UK, there are two main plants that cause primary 18 19Table 1: Common poisonous plants in the UK, grouped by toxic chemicals, describing their common environment, active principle, and clinical signs (Copper & Johnson, 1998; Lynn & Waldren, 2003; Bergero & Nery, 2008; Hastie, 2012) Plant Common environment Active principle Clinical signs ALKALOIDS Poison Hemlock Damp woodland Alkaloid - Coniine Affects Central Nervous System (CNS) - paralysis, convulsion, (Conium maculatum) asphyxia Horse Tails Pastures and damp Piperidine alkaloids Vitamin B deficiency affecting environments and Thiaminase CNS. Mild colic with diarrhoea (Equisetum palustre) enzyme Ragwort Widespread in pasture and Pyrrolizidine alkaloids Chronic effects on liver and wasteland brain (Senecio jacobea) Hound's Tongue Dry soils (Sand, gravel, chalk) Pyrrolizidine alkaloids Liver disease in coastal areas/wasteland (Cynoglossum officinale) Deadly Nightshade Woodland, scrubland Glycoalkaloids Dilated pupils, inflamed mucous membranes. (Atropa belladonna) Affects CNS, excitement, incoordination Woody Nightshade Coastal shingle or woods and Glycoalkaloids Salivation, colic, diarrhoea hedges (Solanum dulcamara) Box plants Ornamental plant Alkaloid Affects CNS and gastrointestinal system. Colic, (Buxus sempervirens) diarrhoea, in-coordination European Yew Evergreen tree or bush, Taxine Alkaloid Sudden death. Less severe usually on chalk affects CNS (Taxus baccata) GLYCOSIDES Foxglove Woods and hillsides Cardiac glycosides Affects CNS - tremors and convulsions. Diarrhoea, colic, (Digitalis purpurea) frequent urination Buttercups Wet soil - marshland and Aglycone - Blister, facial swelling, excess woodlands protoanemonin salivation, mild colic (Ranunculus repens) Bracken Acid soils, moorland, and Thiaminase enzyme Thiamine deficiency – in woodland coordination and in severe (Pteridium aquilinum) cases loss of muscular control TANNINS Oak tree Deciduous tree on clay soil Tannins Gastrointestinal disease is common - can develop into (Quercus robur) kidney or liver conditions PHOTODYNAMIC SUBSTANCES St. John Wort Widespread through Britain Hypericin Photosensitivity and secondary infections in skin lesions (Hypericium perforatum) Buckwheat Occurs on waste ground but Fagopyrin Photosensitivity and dermatitis no a native plant when exposed to sunlight (Fagopyrum esculentum) the digestive tract in several ways (Copper & Johnson, lips), this causes horses to salivate excessively (Marcella, 1998; Stegelmeier & Davis, 2018). When chewed, some 2011; Stegelmeier & Davis, 2018). Following stomatitis, plants can cause mechanical damage to the digestive tract irritation of the stomach and intestines can occur with and cause stomatitis (blistering of tongue, mouth, nose, and clinical signs of abdominal pain, colic, and diarrhoea 20 21processed by the gastrointestinal system, the toxin can developing (Knight & Walter, 2003; Stegelmeier & then also negatively impact the horse’s nervous system Davis, 2018). together with the cardiac system, with no order preference Colic is the most identifiable clinical symptom when (Hastie, 2012). toxic plants are ingested, especially in large quantities, NERVOUS SYSTEM although horse owners may not think the cause is from A neuromuscular junction is a highly specialised toxic plants as there are many other reasons from which structure between a motor neuron nerve terminal and a colic may arise. The potential toxic compound once muscle fibre (Cruz et al., 2020). This junction is responsible absorbed may remain unchanged or it may break down for converting electrical impulses from the motor neuron to spontaneously or undergo enzymatic metabolism (Copper electrical activity in the muscle fibres. However, for muscle & Johnson, 1998). This could lead to colic which may function to occur a neurotransmitter known as acetylcholine imitate plant toxicity by three potential actions: acting as a is required. Acetylcholine crosses the gap from the motor direct irritant to the gastrointestinal system, stimulating the neuron and binds to the receptors on the muscle fibres nervous system to act upon the gastrointestinal tract, and by initiating muscle contraction (Cruz et al., 2020). However, causing obstruction or impaction (Hanson, 2008). when a toxin affecting neurons (neurotoxin) is involved, Buttercups contain glycosides together with the highly this pathway is not completed. R toxic protoanemonin which affects the gastrointestinal E Alkaloids are often associated with affecting the action of P tract (Stegelmeier et al, 2020). Oral irritation is seen as AP nerve transmitters (Copper & Johnson, 1998). The alkaloids blistered lips and stomatitis which results in increased DE atropine and scopolamine are competitive antagonists for L salivation, then as consumption increases and absorption C acetylcholine receptors, therefore interfering with nerve Y takes place, gastroenteritis, colic, and diarrhoea can arise CE impulses reaching cells, and disrupting muscle contraction R with liver disease developing from serious cases (Knight & (Meriney & Fanselow, 2019). The plant Atropa belladonna, %0 Walter, 2003; Stegelmeier et al., 2020). Nightshades also 0 also known as Deadly Nightshade, contains the alkaloids 1 affect the digestive tract as they involve the glycoalkaloid N atropine, hyoscine and scopolamine, making it poisonous O toxin solanine which are particularly potent mucosal and hallucinogenic (Passos & Mironidou-Tzouveleki, DE irritants that commonly cause gastroenteritis, abdominal T 2016). Atropine is also the principal alkaloid found in the NI pain, and diarrhoea (Stegelmeier et al., 2020). However, R Deadly Nightshade´s mature fruits. The fruits are similar P because most toxins may cause extensive multiple organ to berries and are estimated to contain 2mg of atropine, damage, it is imperative to understand all the body systems giving them potent toxicity (Passos & Mironidou- Tzouveleki, 2016). involved in toxicity. After the toxin has been ingested and Rebecca Allan Rebecca moved to England from Spain in 2017 to further her education. While undertaking A levels, she completed BHS Qualifications where she developed a keen interest in equine health and nutrition. In 2019 Rebecca started a BSc (Hons) Veterinary Bioscience degree at the University of Surrey. Rebecca is currently on her placement year as an Assistant Nutritionist at Feedmark Ltd. Her aim is to qualify as a Veterinary Bioscientist and progress into Equine Nutrition in the future. 20 21functions, and it can either consist of a temporary impaired Clinical signs of toxins affecting the nervous systems are functioning of the liver and/or progress to its failure imbalance, changes in heartbeat, uneven muscle contraction whereby the liver loses all or most of its functionality and weakness (Hastie, 2012; Meriney & Fanselow, 2019). (Bergero & Nery, 2008). Pyrrolizidine alkaloid toxicosis CARDIAC EFFECTS is a common cause of liver failure, characterised by liver Cardiac glycosides have a particular effect on the heart, necrosis and fibrosis (Bergero & Nery, 2008). Several as indicated by their name (Copper & Johnson, 1998). case studies have been reported concerning liver disease The heart is controlled by electrical impulses which in horses after consumption of Ragwort (Senecio spp.) are regulated via sodium-potassium pumps. Sodium is and Hound's Tongue (Cynoglossum officinale), both PA actively transported out of the cells whilst potassium is containing plants (Bergero & Nery, 2008) actively transported into the cells, this balance is crucial Following liver damage, cellular lesions can arise for many physiological processes (Pirahanchi et al., whereby hepatic (liver) cells are destroyed (necrosis) or 2021). In addition, there is also a sodium-calcium pump replaced by fibrous connective tissue (fibrosis) (Bergero & regulated by membrane potentials, which generally pumps Nery, 2008; Mair & Love, 2012). Fibrosis is a typical lesion sodium into the cell and calcium out of the cell, under involved with liver dysfunction and occurs when the rate normal circumstances. Calcium is the molecule involved of cell death (necrosis) exceeds the rate of regeneration, in the contraction of the cardiac muscle; therefore, this therefore connective tissue replaces parenchymal sodium-calcium pump indirectly controls this contraction (functional) tissue on the liver surface, effectively impairing (Pirahanchi et al., 2021) the liver (Wynn, 2009). When a toxin such as Digoxin found in Foxglove is The difficulty with liver disease is the non-specific ingested, this toxin binds to the sodium-potassium pump, clinical signs, as they often depend on the severity and inhibiting it and causing an accumulation of sodium duration of the disease (Carlson, 2015). Also at least 80% intracellularly. This increase in sodium levels disturbs or more of the liver must be damaged for clinical signs to the concentration balance within cells, inhibiting sodium- become apparent (Carlson, 2015). Common clinical signs calcium exchange, resulting in increased calcium levels are weight loss, depression, anorexia, and colic, with more within cells (Pirahanchi et al., 2021). Therefore, more liver-specific signs involving hepatic encephalopathy, calcium is available for cardiac contraction. However, as jaundice, and photosensitivity (Carlson, 2015). this increased heart contraction is not a normal physiological response, the body stimulates the Vagus nerve (hearts HEPATIC ENCEPHALOPATHY control mechanism), slowing down conduction between the Hepatic encephalopathy (HE) is a condition where the top and bottom parts of the heart (Pirahanchi et al., 2021), function of the central nervous system is disturbed due resulting in an abnormal heartbeat as contractile strength to hepatic (liver) insufficiency (Bergero & Nery, 2008). has increased and conduction has decreased (Kurian et al., Hepatic encephalopathy is correlated with astrocyte 2015). Prognosis can be positive if the toxin is ingested in (central nervous system cell type) swelling, acute cytotoxic low amounts, nevertheless, cardiac glycosides can cause cerebral swelling, and intracranial hypertension (Divers & haemorrhaging, diarrhoea, and abdominal pain (Copper & Barton, 2018). Johnson, 1998; Hall et al., 2020). Several studies and theories regarding the cause of LIVER DISEASE hepatic encephalopathy exist although only a few have After oral ingestion and gastrointestinal absorption, remained the focus of research and shaped the current toxins pass to the liver, the major organ in which enzymatic approach, although all theories are probably related, and breakdown and detoxification take place (Bergero & Nery, the disease is most likely multifactorial (Mair, 1997). 2008; Carlson, 2015). The term ‘liver disease’ encompasses several pathological conditions that affect the liver’s The blood-brain barrier (BBB) protects the brain from 22 23a wide range of substances as it forms tight junctions skin areas are common, together with blistering of the skin between adjacent endothelial cells of the cerebral (Mair & Love, 2012). Primary photosensitivity is a painful capillaries preventing the passage of unknown substances condition although horses can fully recover if kept out (Skowrońska & Albrecht, 2012). The common derivative of the sun and by removing the plant source (Mair & amongst all theories revolves around the BBB being Love, 2012). compromised due to the liver´s functionality being impaired Secondary photosensitivity develops following liver which then leads to neurological issues (Jones et al., 1984; damage. Phylloerythrin is a bacterial by-product of the Maddison, 1992; Bergero & Nery, 2008; Skowrońska & breakdown of chlorophyll in plants (Stegelmeier, 2002). Albrecht, 2012). Together with alterations in the BBB, Phylloerythrin would be excreted by the liver under normal the liver is also responsible for metabolising amino acids conditions but when liver functionality is impaired, it thus if its functionality is impaired by toxins, amino acid accumulates in the blood reaching the capillaries of the metabolism is also altered (Dejong, et al., 2007). This skin. The Phylloerythrin compound is then activated leads to the additional theory of HE, whereby increased by ultraviolet radiation and causes photosensitivity levels of Aromatic amino acids develop due to decreased (Stegelmeier, 2002). This photosensitivity is commonly liver functionality which impacts neurological systems as observed in subacute to chronic liver diseases, making it they can act as false neurotransmitters (Bergero & Nery, an obvious clinical sign to look out for (Bergero & R 2008). It is therefore a combination of these theories that E Nery, 2008). P can cause HE. AP Taking it all together, many bodily systems are affected D JAUNDICE E by intoxication with some toxins being more prevalent in LC Bilirubin is a breakdown product of red blood cells Y affecting certain organs. Should there be any suspicion of C which passes through the liver to be excreted (Ravindran, E plant poisoning, immediate veterinary attention must be R 2020). However, when liver functionality has been % sought so the problem can be assessed, and the appropriate 00 impaired, Bilirubin is not excreted as efficiently meaning 1 treatment administered (Hastie, 2012). For more N accumulation in the bloodstream occurs. This clinically O information on treatment of liver disease see Liver disease manifests as yellow pigmentations that can be seen in D in horses. What is also essential when an equine poisoning ET non-pigmented skin, mucosal membranes, and the eye's N scenario is encountered, and a key step in managing the IR sclera. This condition is known as jaundice or icterus and is P situation, is preventing further access to the suspected commonly associated with liver disease (Ravindran, 2020). cause of poisoning (Hastie, 2012). PHOTOSENSITIVITY MANAGEMENT Photosensitivity is a clinical syndrome which develops By identifying the key plants and toxins involved in when animals become abnormally reactive to sunlight due to the presence of a phototoxin or photoallergen in their skin (Figure 2) (Collett, 2019). In farm animals, most cases of photosensitivity are due to phototoxins present in pasture plants or preserved forages (Collett, 2019). There are two types of photosensitivity: primary and secondary. Primary photosensitivity is associated with the ingestion of plants containing photodynamic compounds which reach the skin after being absorbed by the gastrointestinal tract (Copper & Johnson, 1998). Plants such as St John’s Wort and Buckwheat contain these compounds and illicit such a Figure 2. Skin lesion due to secondary photosensitivity on horse’s un- response. Erythema (skin rash) and oedema of unpigmented pigmented skin. 22 23equine plant toxicity, together with the clinical signs and body systems affected, a management plant can be developed considering the animal’s husbandry, and physiological and behavioural requirements. Equids are notorious for searching for new green forage which may lead to the consumption of toxic compounds (Webster, 2003). Horse owners should be vigilant for poisonous weeds and plants invading their paddocks and these should be eradicated upon identification. Poisonous trees, such as Oak and Yew trees, should be fenced off appropriately to avoid equines consuming them or their fallen leaves, fruits, and seeds (Hastie, 2012). As for the plants, there is a naturally increased palatability for plants with lower toxins however this does not guarantee the avoidance of highly toxic plant consumption, although secondary toxic metabolites affect Figure 3. Spraying with herbicides is one method of controlling undesirable plants in grazing pasture. Ensure any legal requirements for the taste and smell of the plants and negatively impact purchase, storage, handling and spraying the product are followed and that animals are removed from the pasture as directed by the herbicide their palatability (Copper & Johnson, 1998). Horses in manufacturer. overgrazed paddocks, in poor condition or not supplied with enough food, can find toxic plants appealing and are concern for any horse owner. Although there is no specific more likely to consume them, meaning it is important that characteristic determining a poisonous plant, they can be these plants are eradicated from the grazing area. grouped based on their toxic components, with alkaloids Toxic plants may be eradicated via the following means: posing a major threat to equines. The most common clinical • Physical removal – carefully remove by digging up signs include altered behaviour, colic, neuronal damage, the plant and its roots and dispose of appropriately and muscle loss. Clinical signs are varied due to the various • Spraying with a herbicide – this method is more body systems being affected starting at the gastrointestinal invasive, and horses must be removed from the tract through to the liver. In severe cases, damage to the liver immediate and surrounding area before spraying can cause further issues such as hepatic encephalopathy is carried out. Keeping animals off the area after affecting the central nervous system, together with jaundice spraying is also usually required so it is advised to and photosensitivity. As soon as a horse experiences a toxic check the herbicide manufacturers' exclusion period event, veterinary attention is imperative to help manage before returning animals to the area (Figure 3). the horse’s condition and decide the best course of action. Ornamental garden plants such as Rhododendron, Privet Management procedures to minimise toxic events from and Yew should also be considered as sources of toxins occurring must be put in place whereby toxic plants should (Hastie, 2012). These plants may border the grazing area, be eradicated once visualised. Thus, enabling horse owners be encountered whilst hacking, or be consumed if your horse or pony is kept at home with access to your garden. to establish a balance between the mere presence of toxic plants and their over-abundance, keeping horses safe, and SUMMARY free from unfortunate toxic events. Consumption of poisonous plants is a cause for 24 25REFERENCES Anadón, A., Martínez-Larrañaga, M.R. & Castellano, V. (2012). Poisonous plants of Europe. In: Veterinary Toxicology: Basic and Clinical Principles, 2nd edition. Elservier: London Berny, P., Caloni, F., Croubels, S., Sachana, M., Vandenbroucke, V., Davanzo, F. & Guitart, R. (2010). Animal poisoning in Europe. Part 2: Companion animals. Veterinary Journal, 183: 255-259. Bergero, D. & Nery, J. (2008). Hepatic diseases in horses. Journal of Animal Physiology and Animal Nutrition, 92: 345-355 Carlson, K.L. (2015). Hepatic disease in the horse. In: Sprayberry, K.A. & Robinson, E.N. (eds.). Robinson´s current therapy in equine medicine. 7th edition. Elservier Saunders: USA. Cooper, M.R. & Johnson, A.W. (1998). Poisonous principles. In: Poisonous plants and Fungi in Britain; Animals and human poisoning. 2nd Edition. The Stationary Office: London Cramer, L., Ernst, L., Lubienski, M., Papke, U., Schiebel, H.M., Jerz, G. & Beuerle, T. (2015). Structural and quantitative analysis of Equisetum alkaloids. Phytochemistry, 115: 27-37. Crews, C. & Anderson, W.A.C. (2009). Detection of ragwort alkaloids in toxic hay by liquid chromatography/ time of flight mass spectrometry. Veterinary Records, 165: 568-569 Collett, M. G. (2019). Photosensitisation diseases of animals: Classification and a weight of evidence approach to primary causes. Toxicon: X, 3:100012. Cruz, P.M.R., Cossins, J., Beeson, D. & Vincent, A. (2020). The neuromuscular junction in health and disease: molecular mechanisms governing synaptic formation and homeostasis. Frontiers in Molecular Neuroscience, 13: 610964 Dalefield, R. (2017). Chapter 24 - Poisonous Plants. In: Kruze, Z. (eds.). Veterinary Toxicology for Australia and New Zealand. Elsevier: UK Dejong, C.H.C., van de Poll, M.C.G., Soeters, P.B., Jalan, R. & Damink, S.W.M. (2007). Aromatic Amino Acid metabolism during liver failure. The Journal of Nutrition, 137(6): 1579-1585 Hall, A.L., Gornish, E. & Ruyle, G. (2020). Poisonous plants on rangelands. The University of Arizona Cooperative Extension, az1828: 1-10. Hanson, G. (2008). The toxicity of plants in equines: A modern three-point approach to disseminating information (PhD Thesis). University of Idaho: USA Hastie, P.S. (2012). Poisons and Poisoning (Toxicology). In: Ivens, P. (eds.). The BHS Veterinary Manual. 2nd Edition. Kenilworth Press: UK Heinrich, M., Mah, J., & Amirkia, V. (2021). Alkaloids used as medicine: Structural Phytochemistry Meets Biodiversity. Molecules. 26(7):1836. James, L.F., Gardner, D.R., Lee, S.T., Panter, K.E., Pfister, J.A., Ralphs, M.H., & Stegelmeier, B.L. (2005). Important poisonous plants on rangelands. Rangelands, 27:3-7. Jones, E. A., Schafer, D. F., Ferenci, P., & Pappas, S. C. (1984). The GABA hypothesis of the pathogenesis of hepatic encephalopathy: current status. The Yale Journal of Biology and Medicine, 57(3): 301–316. Jou, J. H., Lin, C. C., Li, T. H., Li, C. J., Peng, S. H., Yang, F. C., Thomas, K., Kumar, D., Chi, Y., & Hsu, B. D. (2015). Plant Growth Absorption Spectrum Mimicking Light Sources. Materials, 8(8):5265–5275. Knight, A.P. & Walter, R.G. (2003). Plants affecting the digestive system. International Veterinary Information Service, B0503.1102: 1-42. Kurian, M. (2015). The Effect of Digitalis on the Heart – An Update. Journal of Pharmaceutical Sciences and Research, 7(10): 861 – 863. R Loh, Z. H., Ouwerkerk, D., Klieve, A. V., Hungerford, N. L., & Fletcher, M. T. (2020). Toxin Degradation by Rumen Microorganisms: A Review. Toxins, 12(10):664. EP Lynn, D.E. & Waldren, S. (2003). Survival of Ranunculus repens L. (Creeping Buttercup) in an Amphibious Habitat. Annals of Botany, 91(1):75-84. AP Maddison, J.E. (1992). Hepatic encephalopathy. Current concepts of the pathogenesis. Journal of Veterinary Internal Medicine, 6(6):341-353 D Mair, T.S. (1997). Ammonia and encephalopathy in the horse. Equine Veterinary Journal, 29(1): 1-2 E Mair, T. S. & Love, S. (2012). Chapter 22 - Metabolic Diseases and Toxicology. In: Schumacher, J., Smith, R. & Frazer, G.S. (eds.). Equine Medicine, Surgery and Reproduction. LC 2nd Edition. Elsevier Ltd: China. Y Mair, T. S., & Love, S. (2012). Gastroenterology: Hepatic and intestinal disorders. Equine Medicine, Surgery and Reproduction, PMC7150257: 49–65. CE Majak, W. (2001). Review of toxic glycosides in rangelands and pasture forages. Journal of Range Management, 54(4): 494-498. R Marcella, K. (2011). Stomatitis and excessive salivation in horses. Doctor of Veterinary Medicine 360, 42(4). % Matsuura H.N. & Fett-Neto A.G. (2015) Plant Alkaloids: Main Features, Toxicity, and Mechanisms of Action. In: Gopalakrishnakone P., Carlini C., Ligabue-Braun R. (eds.). Plant 00 Toxins. Toxicology. Springer: Netherlands. 1 Meriney, S.D. & Fanselow, E.E. (2019). Chapter 16: Acetylcholine. In: Synaptic Transmission, Elsevier: UK N Norman, T.E., Chaffin, M.K., Norton, P.L., Coleman, M.C., Stoughton, W.B. & Mays, T. (2012). Concurrent Ivermectin and Solanum spp. Toxicosis in a Herd of Horses. Journal of O Veterinary Internal Medicine, 26: 1439-1442. DE Ober, D., & Hartmann, T. (1999). Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase. T Proceedings of the National Academy of Sciences of the United States of America, 96(26): 14777–14782. NI Panter, K.E., Gardner, D.R., Lee, S.T., Pfister, J.A., Ralphs, M.H., Stegelmier, B.L. & James, L.F. (2012). Poisonous plants of the United States. In: Gupta, R.C., Veterinary Toxicology: RP Basic and Clinical Principles. 2nd edition. Elsevier Inc: USA Passos, I.D. & Mironidou-Tzoueleki, M. (2016). Hallucinogenic plants in the Mediterranean countries. In: Preedy, V.R. (eds.). Neuropathology of drug addictions and substance misuse. Volume 2. Elsevier: Kings College London Pavarini, D.P., Pavarini, S.P., Niehues, M. & Lopes, N.P. (2012). Exogenous influences on plant secondary metabolite levels. Animal Feed Science and Technology, 174 (1-4): 5-16. Pfister, J.A., Molyneux, R.J. & Baker, D.C. (1992). Pyrrolizidine alkaloid content of houndstongue (Cynoglossum officinale L.). Journal of Range Management, 45: 254-256. Pfister, J.A., Panter, K.E., Gardner, D.R., Stegelmier, B.L., Ralphs, M.H. & Molyneux, R.J. (2001). Alkaloids as anti-quality factors in plants on western U.S. rangelands. Journal of Range Management, 54: 447-461. Pirahanchi, Y., Jessu, R. & Aeddula, N.R. (2021). Physiology, Sodium Potassium Pump. StatPearls Publishing, 30725773. Ravindran, R. (2020). Jaundice. Hepatobiliary Surgery, 38(8):446-452 Divers, T.J. & Barton, M.H. (2018). Disorders of the liver. In: Reed, S.M., Bayly, W.M. & Sellon, D.C. (eds.). Equine Internal Medicine. 4th Edition. Elservier: USA Sestric, E. & Coates-Markle, L. (2005). Keeping your horse healthy. Oregon State University Extension Service Bulletin, EC-1472:1-5. Skowrońska, M. & Albrecht, J. (2012). Alterations of blood-brain barrier function in hyperammonaemia: an overview. Neurotoxicity Research, 21(2):236-244 Stegelmeier, B.L. (2002). Equine Photosensitization. Clinical Techniques in Equine Practices, 1(2): 81-88 Stegelmeier, B.L. (2011). Pyrrolizidine alkaloid – Containing Toxic Plants (Senecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium, and Echium spp.). Veterinary Clinics of North America: Food Animal Practice, 27(2): 419-428. Stegelmeier, B.L. & Davis, T.Z. (2018). Toxic Causes of Intestinal Disease in Horses. In: Stämpfli, H., Schoster, A. & Divers, T.J. Recent Advances in the Diagnosis and Management of Equine Gastrointestinal Diseases. Volume 34, Elsevier: USA. Stegelmeier, B.L., Davis, T.Z. & Clayton, M.J. (2020). Plants containing Urinary tract gastrointestinal, or miscellaneous toxins that affect livestock. Veterinary Clinics of North America: Food Animal Practice, 36(3):701-713 Vandenbroucke, V., van Pelt, H., de Backer, P. & Croubels, S. (2010). Animal poisoning in Belgium: A review of the past decade. Vlaams Diegeneeskund. Tijdschr, 79: 259-268. Van Raamsdonk, L.W., Ozinga, W.A., Hoogenboom, L.A., Mulder, P.P., Mol, J.G., Groot, M.J., van der Fels-Klerx, H.J. & de Nijs, M. (2015). Exposure assessment of cattle via roughages to plants producing compounds of concern. Food Chemistry, 189:27-37. Webster, J. (2013). Audits of animals in agriculture. In: Animal Husbandry Regained, The place of farm animals in sustainable agriculture. Taylor and Francis Group: USA. Wynn, T. (2008) Cellular and molecular mechanisms of fibrosis. The Journal of Pathology, 214 (2):199–210. Zentek, J., Aboling, S. & Kamphues, J. (1999). Accident report: Animal nutrition in veterinary medicine actual cases: Houndstongue (Cynoglossum officinale) in pasture – A health hazard to horses. Deutsche Tierarztliche Wochenschrift, 106(11):475-477. 24 25Ingredient spotlight: Turmeric Anouk Frieling, MSc Equine Sciences, BSc (Hons) Turmeric, also known as the golden spice due to its yellow colour, is an equine supplement that is commonly used due to its supportive functions in the body. For many years turmeric has been used as a health product for humans to soothe health issues such as abdominal pains, sinusitis, sprains and swellings. Turmeric has also been shown to have anti-inflammatory, anti-parasitic and antimicrobial effects in humans. More recently, research studies have Figure 1. Turmeric is a rhizome from the Curcuma longa plant. Turmeric evaluated the beneficial effects of turmeric supplements in owes its yellow colour to the curcuminoid curcumin, which is one of the composites in turmeric. Due to the yellow/golden colour of turmeric and equine nutrition. Therefore, this article will focus on the the many beneficial functions it is also known as ‘the golden spice’. composition, bioavailability and health benefits of turmeric have shown to have anti-cancerous properties in humans as an equine supplement. (Yodkeeree et al., 2009). Curcumin is the main active COMPOSITION OF TURMERIC component and the most abundant curcuminoid, comprising The spice turmeric originates from South Asia and is a 2 to 5% of turmeric. It is also the component that gives rhizome of the Curcuma longa plant (Ali et al., 2014), which turmeric its bright yellow colour (Gupta et al., 2013a). is related to the ginger family (Gupta, et al., 2013b) (Figure TURMERIC BIOAVAILABILITY 1). For humans the spice is distributed in many forms such Both turmeric in its whole form and extracts of as ground turmeric powder (loose or in capsules), turmeric curcumin have poor bioavailability and therefore only a extract, turmeric tea and turmeric oil and is also often used small portion of the ingredient will be directly absorbed for cooking purposes. Turmeric supplements for horses are in the small intestine that can be used for biological mainly distributed in the form of turmeric powder or oil and activities (Shishu & Maheshwari, 2010; Aller, 2019). are ingested orally. Not every horse is instantly fond of the Besides poor bioavailability, turmeric and curcumin bitter taste of turmeric powder and therefore the powdered become unstable at a physiological pH, are insoluble in form of turmeric should be introduced gradually in the diet water, are absorbed very slowly by body cells and are so that the horse can get used to the taste. rapidly metabolised in the body (Siviero et al., 2015). Currently 235 different compounds in turmeric have Studies have compared the individual bioavailability been identified through research (Li, 2011). From these 235 of whole turmeric and curcumin extract. Turmeric had a components, curcuminoids (part of the diarylheptanoids greater significant effect on pro-inflammatory genes and components) have been recognised as the active feeding turmeric resulted in a higher level of curcumin in components (Meng et al., 2018). Turmeric contains three the digestive tract than when feeding a curcumin extract, types of curcuminoids: curcumin, demethoxycurcumin suggesting that turmeric is more stable and bioavailable and bisdemethoxycurcumin (Kotra et al., 2019). All (Martin et al., 2012). Turmeric is curcumin's precursor and three curcuminoids have been studied separately to therefore consists of multiple components, as mentioned gather better understanding about their function in the before. These other components, in combination with body. Demethoxycurcumin and bisdemethoxycurcumin 26 27curcumin, are more resistant against rapid metabolisation 500kg, reduces severe gastric ulcers caused by dietary in the body, which explains why whole turmeric is more change and does not create or worsen them. bioavailable (Martin et al., 2012). Even though turmeric As mentioned before turmeric has an effect on pro- has a higher bioavailability than curcumin extract, there inflammatory genes (Martin et al., 2012). Turmeric reduces has been an interest in increasing the bioavailability of the pro-inflammatory cytokines tumor necrosis factor-alpha turmeric to improve the effects of supplementing this (TNF-α) and interleukin-1β (IL-1β), which are related spice. A common ingredient that is added to turmeric and to osteoarthritis and therefore supplementing turmeric increases bioavailability is piperine, the active component works positively for horses with joint issues (Farinacci of black pepper (Figure 2). Shoba et al. (1998) found that et al., 2009). Due to reducing inflammatory responses, supplementing a combination of curcumin and piperine to turmeric may also provide pain relief to horses that suffer rats, increased blood curcumin levels compared to levels from osteoarthritis. after only supplementing curcumin. Adding lipids, such as In humans turmeric has also shown to have anti-parasitic linseed oil, has also shown to have a positive effect on the purposes. Unfortunately, studies have not been able to bioavailability of turmeric (Chang et al., 2013; Mohammed confirm the same effect after supplementation to horses et al., 2021). Therefore, it is commonly advised to feed oils (Wuest et al., 2017). R in combination with turmeric to the horse to optimise the EPA supplement's effect. P DE EFFECTS OF TURMERIC SUPPLEMENTATION ON TURMERIC FEEDING GUIDE LC THE HORSE YC • Feed turmeric with black pepper or piperine E Turmeric has been used for many years as a health R • Feed turmeric in combination with lipids such as % product for humans and more recently is also distributed 0 linseed oil 01 as an equine supplement as research in horses has analysed • Gradually increase daily amount so that horses NO can get used to the taste and evaluated the positive effects of turmeric. For example, DE turmeric supplementation has been associated with the TNI reduction of gastric acid in the stomach which causes RP Supplementation of turmeric has also shown to have gastric ulcers in horses (Fletcher & Gough, 2019). Fletcher an effect on the microbiome abundances of rats (Han et & Gough (2019) demonstrated that supplementation of 20 al., 2020). Rats are small hindgut fermenters and share grams of turmeric powder, to adult horses weighing about similar microbiome abundances with horses (Han et al., 2018). For that reason, there has been an interest to study the effect of turmeric on the hindgut of the horse. Results of the small number of studies suggest that turmeric alters caecal characteristics such as the total volatile fatty acid production (VFA) (Bland et al., 2017). Future research is needed to be able to identify the effect turmeric has when it reaches the hindgut and the microbiome. SUMMARY Figure 2. To increase bioavailability studies have analysed the Turmeric has been an established supplement for human effects of adding piperine and lipids. Both have shown to improve the consumption and has become a popular equine supplement bioavailability of turmeric and curcumin. 26 27in recent years. The working component of turmeric is has shown to have many beneficial effects. The equine curcumin. Both whole turmeric and curcumin extract have supplement is primarily known for its anti-inflammatory poor bioavailability. Research has shown that combining properties and ability to reduce gastric acid in the stomach. turmeric and curcumin with black pepper, piperine or There is an interest to further analyse the effect of turmeric lipids increases this bioavailability and therefore allows on the hindgut and further research will be needed to the supplement to work optimally. In humans turmeric measure these effects. Anouk Frieling, MSc Equine Sciences, BSc (Hons) Anouk has been involved with horses from a young age. During her time taking care of horses on yards and during the undergraduate Animal Husbandry at HAS University of Applied Sciences in the Netherlands, she developed an interest for equine nutrition. To gain more specific knowledge about equine nutrition she completed the MSc Equine Sciences at Aberystwyth University. As Senior Nutritionist at Feedmark, Anouk provides information that combines her technical knowledge and practical experience obtained from her studies and taking care of many different types of horses. REFERENCES Ali, I., Haque, A., & Saleem, K. (2014). Separation and identification of curcuminoids in turmeric powder by HPLC using phenyl column. Analytical Methods, 2014(8): 2526-2536. Aller, L. L. (2019). What about bioavailability of oral curcumin? Canadian Medical Association Journal 191(15): E427. Bland, S. D., Venable, E. B., McPherson, J. L., & Atkinson, R. L. (2017). Effects of liposomal-curcumin on five opportunistic bacterial strains found in the equine hindgut - preliminary study. Journal of Animal Science and Technology, 59(1): 2-5. Chang, M. T., Tsai, T. R., Lee, C. Y., Wei, Y. S., Chen, Y. J., Chen, C. R., & Tzen, J. T. C. (2013). Elevating bioavailability of curcumin via encapsulation with a novel formulation of artificial oil bodies. Journal of Agricultural and Food Chemistry, 61(40): 9666-9671. Farinacci, M., Gaspardo, B., Colitti, M., & Stefanon, B. (2009). Dietary administration of Curcumin modifies transcriptional profile of genes involved in inflammatory cascade in horse leukocytes. Italian Journal of Animal Science, 8(2): 84-86. Gupta, S. C., Kismali, G., & Aggarwal, B. B. (2013a). Curcumin, a component of turmeric: From farm to pharmacy. BioFactors, 39(1): 2-13. Gupta, S. C., Sung, B., Kim, J. H., Prasad, S., Li, S., & Aggarwal, B. B. (2013b). Multitargeting by turmeric, the golden spice: From kitchen to clinic. Molecular Nutrition and Food Research, 57(9): 1510-1528. Han, K. H., Jibiki, T., & Fukushima, M. (2020). Effect of Hydrothermal Treatment of Depigmented Turmeric (Curcuma longa L.) on Cecal Fermentation in Rats. Starch, 72(5-6): 1900221. Han, K., Jin, W., Mao, Z., Dong, S., Zhang, Q., Yang, Y., Chen, B., Wu, H., & Zeng, M. (2018). Microbiome and butyrate production are altered in the gut of rats fed a glycated fish protein diet. Journal of Functional Foods, 47: 423-433. Kotra, V. S. R., Satyabanta, L., & Goswami, T. K. (2019). A critical review of analytical methods for determination of curcuminoids in turmeric. Journal of Food Science and Technology 56(12): 5153-5166. Li, S. (2011). Chemical Composition and Product Quality Control of Turmeric (Curcuma longa L.). Pharmaceutical Crops, 5(1): 28-54. Martin, R. C. G., Aiyer, H. S., Malik, D., & Li, Y. (2012). Effect on pro-inflammatory and antioxidant genes and bioavailable distribution of whole turmeric vs curcumin: Similar root but different effects. Food and Chemical Toxicology, 50(2): 227-231. Meng, F.-C., Zhou, Y.-Q., Ren, D., Wang, R., Wang, C., Lin, L.-G., Zhang, X.-Q., Ye, W.-C., & Zhang, Q.-W. (2018). Turmeric: A Review of Its Chemical Composition, Quality Control, Bioactivity, and Pharmaceutical Application. Natural and Artificial Flavoring Agents and Food Dyes, 2018: 299-350. Mohammed, H. E., Attiyah, S. M., & Atta, S. A. (2021). Comparative study on the pro-inflammatory activity of turmeric (Curcuma longa) and flaxseed (linumusitatissimum). Annals of the Romanian Society for Cell Biology, 25(4): 6329-6335. Shishu, & Maheshwari, M. (2010). Comparative bioavailability of curcumin, turmeric and BiocurcumaxTM in traditional vehicles using non-everted rat intestinal sac model. Journal of Functional Foods, 2(1): 60-65. Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R., & Srinivas, P. S. S. R. (1998). Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica, 64(4): 353-356. Siviero, A., Gallo, E., Maggini, V., Gori, L., Mugelli, A., Firenzuoli, F., & Vannacci, A. (2015). Curcumin, a golden spice with a low bioavailability. Journal of Herbal Medicine, 5(2): 57-70 Fletcher SPS., & Gough, SL. (2019). Pre-Treatment with Turmeric (C. Xanthorrhiza) Reduces the Severity of Squamous Gastric Ulceration in Feed Restricted Horses. Journal of Animal Science and Research, 3(1): 1-6. Wuest, S., Atkinson, R. L., Bland, S. D., & Hastings, D. (2017). A Pilot Study on the Effects of Curcumin on Parasites, Inflammation, and Opportunistic Bacteria in Riding Horses. Journal of Veterinary Equine Science, 57: 46-50. Yodkeeree, S., Chaiwangyen, W., Garbisa, S., & Limtrakul, P. (2009). Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA. Journal of Nutritional Biochemistry, 20(2): 87-95. 28 29Appendix 1: Common plants in the UK poisonous to equids Common Common Plant image Latin name Plant image Latin name name name Buxus Cynoglossum Box plant Hounds sempervirens officinale Tongue Pteridium Quercus robur Bracken fern Oak tree aquilinum Fagopyrum Conium Buckwheat Poison R esculentum maculatum E Hemlock PAP DELCYC Ranunculus Ligustrum Buttercups Privet ER repens ovalifolium %001 NO DE Atropa Senecio Deadly Ragwort T belladonna jacobea N Nightshade IRP Taxus baccata Rhododendron European Rhododen- spp Yew dron Digitalis Hypericium Foxglove St. John purpurea perforatum Wort Equisetum Solanum Horsetails Woody palustre dulcamara Nightshade 28 29Glossary The non-sugar component of a glycoside molecule that results from the hydrolysis Aglycone (splitting) of a molecule. Anti-inflammatory A substance to reduce inflammation in the body. Antimicrobial A substance that reduces the growth of unwanted microorganisms. Anti-parasitic A substance used to reduce parasitic infections. An abundant cell type forming part of the central nervous system (CNS) which Astrocytes performs a variety of tasks, from axon guidance and synaptic support to the control of the blood-brain barrier and blood flow. A yellow pigment that passes through the liver and is excreted out of the body. High Bilirubin substances can indicate liver problems. The amount of the substance that is able to enter the circulation and have an effect on Bioavailability the body. Cytotoxic The quality of being toxic to cells. Endocrinopathic A disease or disorder of the endocrine system. Simple columnar epithelial cells which line the inner surface of the small and large Gastrointestinal enterocytes intestines playing a key role in the absorption of molecules from the gut lumen. Organic compounds with a ring structure, containing at least one carbon atom in the Heterocyclic ring ring and at least one other element, such as Nitrogen, Oxygen or Sulphur. Intracranial hypertension The build-up of pressure around the brain. Metabolite Chemical compounds produced by cells through metabolic pathways. A double membrane organelle which can be found in animal cells and is associated Mitochondria with the biochemical processes of respiration and energy production. Molecules used by the nervous system to transmit messages between neurons, or from Neurotransmitters neurons to muscles. Often referred to as the body´s chemical messengers. A degenerative disease that affects joint cartilage and underlying bone structures Osteoarthritis which can cause stiffness and pain. Oxidation A reaction in the body, requiring oxygen, in which a compound loses electrons. Phototoxin A substance that is rendered toxic or more toxic in the presence of light. A chemical compound mixture formed through polymerisation and mainly consisting Polymer of repeating structural units. Rhizome A continuously growing underground stem from a plant. Inflammation of the mucous membranes of the mouth, including the inner aspects Stomatitis such as the nose, lips, tongue, and throat. Toxins Substances that are toxic to the animal. Triglycerides An ester formed form three fatty acid groups and glycerol. Main nerve of the parasympathetic nervous system (relaxing state), playing a key Vagus nerve role in the regulation of the beat-to-beat control of heart rate, acting to lower the heart rate. 30 31Hungry for knowledge? REPAP DELCYC To get every edition of The JEN ER to your inbox for free, sign up today at %001 feedmark.com/JEN NO DETNIRP You will receive no marketing literature, and you will be the first to receive The JEN! 30 31® Feedmark 43 YEARS AT THE CENTRE OF EQUINE NUTRITION 32 PB