Metabolites are small molecules involved in the metabolic processes within a horse's body. They are the intermediates and products of metabolism, encompassing a wide range of compounds, such as amino acids, lipids, carbohydrates, and nucleotides. These molecules play roles in energy production, growth, and cellular repair. The study of equine metabolites, often conducted through metabolomics, provides insights into the physiological and pathological states of horses. Changes in metabolite levels can indicate alterations in metabolic pathways, potentially reflecting health conditions or responses to environmental factors. This page compiles peer-reviewed research studies and scholarly articles that explore the identification, function, and diagnostic potential of metabolites in equine health.
Ishii H, Shigematsu R, Takemoto S, Ishikawa Y, Mizobe F, Nomura M, Arima D, Kunii H, Yuasa R, Yamanaka T, Tanabe S, Nagata SI, Yamada M, Leung GN.Osilodrostat, used to treat Cushing's disease, exhibits an anabolic effect, leading to its classification as a prohibited substance in horseracing and equestrian sports. This study reports the characterization of osilodrostat metabolites in horse urine and elucidates its metabolic pathways for the first time for doping control purposes. Methods: Osilodrostat was administered nasoesophageally to four thoroughbreds (one gelding and three mares) at a dose of 50 mg each. Potential metabolites were extensively screened via our developed generic approach employing differential analysis to identify m...
Kerley BS, Harris P, Lea K, McClendon M, Adams AA.Forage low in nonstructural carbohydrates (NSC) is recommended for insulin dysregulated (ID) horses, indicating the importance of an accurate forage analysis. However, it remains to be fully understood how handling forage samples pre-analysis impacts nutrient values. The objective of this study was to compare the effect of fresh-forage storage-handling methods: microwave-oven (MO; 9kw; 70s then stored at -20℃), room temperature (20℃), 3℃, -20℃, and -80℃. Subsamples collected from a mixed-grass pasture and a ryegrass plot were analyzed for crude protein (CP), water soluble carbohydrat...
Li X, Du M, Liu Y, Wang M, Shen Y, Xing J, Zhang L, Zhao Y, Bou G, Bai D, Dugarjaviin M, Xia W.During follicular development, changes in the composition of the follicular fluid are synchronized with the development of oocytes. Our aim was to screen the key factors affecting oocyte maturation and optimize the in vitro culture protocol by understanding the changes of proteins and metabolites in follicular fluid. Follicles are divided into three groups according to their diameter (small follicle fluid (SFF): 10 mm < d < 20 mm; medium follicle fluid (MFF): 20 mm < d < 30 mm; large follicle fluid (LFF): 30 mm < d). Proteins and metabolites from the follicular fluid w...
Becerro-Rey L, Martín-Cano FE, Fabres Robaina Sancler-Silva Y, Gil MC, Ortega-Ferrusola C, Aparicio IM, Gaitskell-Phillips G, da Silva-Álvarez E....Conservation of equine semen in the liquid state is a central procedure in horse breeding and constitutes the basis of associated reproductive technologies. The intense mitochondrial activity of the stallion spermatozoa increases oxidative stress along the storage period, leading to sperm demise within 24-48 h of storage, particularly when maintained at room temperature. Recently, the relationship between metabolism and oxidative stress has been revealed. The study aimed to extend the period of conservation of equine semen, at room temperature through modification of the metabolites present i...
Lashkari S, Beblein C, Christensen JW, Jensen SK.High-starch diets may affect equine hindgut microbiota and increase blood glucose levels, which may cause unwanted physiological changes, but may also elicit behavioural changes such as increased fear reactions. The purpose of the current study was to feed a high starch (300) and low fat (43; HS_LF) or a low starch (60) and high fat (85; LS_HF, g/kg of DM) concentrate within the available commercial range and investigate how muscle endurance and fear reactions of horses respond to different diets. Twenty Danish Warmblood stallions (4 years) were randomly allocated to two treatments: LS_HF (n...
Goudet G, Beauclercq S, Douet C, Reigner F, Deleuze S, Nadal-Desbarats L.Successful reproductive management of domestic mammals depends primarily upon timely identification of oestrous cycle stages. There is a need to develop an alternative non-invasive, welfare-friendly, accurate and reliable method to identify reproductive cycle stages. This is of particular interest for horse breeders, because horses are high-value farm animals that require careful management and individual monitoring. Saliva sampling is non-invasive, painless and welfare-friendly. Thus, we performed a metabolomic analysis of equine saliva during different reproductive stages to identify changes...
Takahashi K, Mukai K, Ebisuda Y, Sugiyama F, Yoshida T, Hatta H, Kitaoka Y.Evidence suggests that positive pacing strategy improves exercise performance and fatigue tolerance in athletic events lasting 1-5 min. This study investigated muscle metabolic responses to positive and negative pacing strategies in Thoroughbred horses. Eight Thoroughbred horses performed 2 min treadmill running using positive (1 min at 110% maximal O uptake [V̇Omax], followed by 1 min at 90% V̇Omax) and negative (1 min at 90% V̇Omax, followed by 1 min at 110% V̇Omax) pacing strategies. The arterial-mixed venous O difference did not significantly differ between the two strategies. Pl...
Cutler C, Viljanto M, Hincks P, Habershon-Butcher J, Scarth J, van Eenoo P.S-23 is an arylpropionamide selective androgen receptor modulator that has been investigated in animal models for use as a male hormonal contraceptive but is not yet available therapeutically. S-23 is available alongside other selective androgen receptor modulators (SARMs) to purchase online via uncontrolled sites, sold as supplement products. It has been detected in several human doping cases, highlighting the importance of identifying the best analytical targets for equine doping control. The purpose of this study was to investigate the detection of S-23 and its phase I metabolites in equine...
Kabi L E, Zor TA, Göktaş EF, Güneş E, Yatanaslan L, Tektaş MH, İnceman B, Tufan M.The use of prohibited substances in horse racing is a major concern that jeopardizes both the fairness of competitions and the health of horses. This problem can stem from the use of licensed drugs for animal health, as well as unlicensed substances. Horse doping laboratories monitor the potential use of these substances in racehorses within the framework of regulations set by the International Federation of Horse Racing Authority. In this context, sildenafil and its major metabolite n-desmethyl sildenafil were detected in a post-race horse urine sample sent to the Pendik Veterinary Control In...
Hisaeda K, Ono T, Kadekaru S, Hata A, Miyama TS, Kutara K, Sugimoto K, Hiasa Y, Ohzawa E, Kunieda T, Iwata E, Kitagawa H.Plasma or serum amino acids are used to evaluate nutritional status and metabolic disorders. In this study, we aimed to set reference values of serum amino acid concentrations in the Noma horse, a Japanese native horse. Thirty-one horses were classified into six age groups: neonatal foal (0-4 days), foal (0.5-1 years), youth (5 years), middle age (10 years), old (15 years), and extra-old (>20 years). Horses >5 years of age were analyzed together as the adult group. In the adult horses, there were no significant differences among the serum amino acid concentrations of each age group. The ...
Muñoz-Prieto A, Llamas-Amor E, Cerón JJ, Hansen S.Equine gastric ulcer syndrome (EGUS) is a prevalent condition in horses, affecting up to 93% of racehorses. Comprising the equine squamous gastric disease (ESGD) and the equine glandular gastric disease (EGGD), EGUS poses significant health challenges. Saliva, a non-invasive and easily obtainable sample, is increasingly recognized for its potential as a source of biomarkers in horses. This study investigates changes in saliva analytes using automated assays before and after EGUS treatment, aiming to identify biomarkers indicative of treatment success or failure. A total of 28 horses diagnosed ...
Ho HSM, Farrington AF, Bond AJ, Ho ENM, Wong WT.Estra-4,9-diene-3,17-dione (dienedione) is an anabolic-androgenic steroid (AAS) available on the market as a dietary supplement for bodybuilding. It is prohibited in both human and equine sports due to its potential performance-enhancing effect. With the rare presence of the 4,9-diene configuration in endogenous steroids, dienedione has been considered as a synthetic AAS. Nevertheless, the reoccurring detection of dienedione in entire male horse urine samples led to the investigation of its possible endogenous nature in horses, and its endogenous nature in entire male horses has been recently ...
Kilcoyne I, Nieto J, Nottle BF, Flynn H, Knych HK.Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb. Objective: The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin. Methods: Randomised cross-over in vivo experiment. Methods: Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2-week washout per...
Asahi Y, Arai T, Tanaka Y.In older horses, basal metabolic rate decreases, and plasma metabolite and hormone concentrations related to energy metabolism change. The occurrence of age-related diseases, which increases in old animals, may enhance inflammatory reactivity (inflammaging). Finding the appropriate treatment for inflammaging at an early stage may prevent various age-related diseases. Changes in metabolite and hormone concentrations and enzyme activities involved in energy metabolism in the plasma of clinically healthy riding horses of various ages were measured to identify biomarkers of inflammaging (persisten...
Mady EA, Osuga H, Toyama H, El-Husseiny HM, Inoue R, Murase H, Yamamoto Y, Nagaoka K.The gut microbiota (GM) is essential for mammalian health. Although the association between infant GM and breast milk (BM) composition has been well established in humans, such a relationship has not been investigated in horses. Hence, this study was conducted to analyze the GM formation of foals during lactation and determine the presence of low-molecular-weight metabolites in mares' BM and their role in shaping foals' GM. The fecal and BM samples from six pairs of foals and mares were subjected to 16S ribosomal RNA metagenomic and metabolomic analyses, respectively. The composition of foal G...
Kwak YB, Yoon J, Yoo HH.SR9009, a peroxisome proliferator-activated receptor δ (PPARδ) agonist, is known for its potential benefits in energy homeostasis. It failed to receive the United States Food and Drug Administration (USFDA) approval and its illegal distribution has raised concerns. As a result, it has been classified as a prohibited substance by the World Anti-Doping Agency and the International Federation of Horseracing Authorities (IFHA). This study emphasizes the application of the in-silico molecular networking technology to analyze phase I drug metabolites in horses, distinguishing it from conventional ...
Whitfield-Cargile CM, Chung HC, Coleman MC, Cohen ND, Chamoun-Emanuelli AM, Ivanov I, Goldsby JS, Davidson LA, Gaynanova I, Ni Y, Chapkin RS.The equine gastrointestinal (GI) microbiome has been described in the context of various diseases. The observed changes, however, have not been linked to host function and therefore it remains unclear how specific changes in the microbiome alter cellular and molecular pathways within the GI tract. Further, non-invasive techniques to examine the host gene expression profile of the GI mucosa have been described in horses but not evaluated in response to interventions. Therefore, the objectives of our study were to (1) profile gene expression and metabolomic changes in an equine model of non-ster...
You Y, Missanelli JR, Proctor RM, Haughan J, Robinson MA.Oxycodone, an opioid commonly used to treat pain in humans, has the potential to be abused in racehorses to enhance their performance. To understand the pharmacokinetics of oxycodone and its metabolites in horses, as well as to detect the illegal use of oxycodone in racehorses, a method for quantification and confirmation of oxycodone and its metabolites is needed. In this study, we developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method that can simultaneously quantify and confirm oxycodone and eight metabolites in equine urine. Sa...
Thomson ACS, McCarrel TM, Zakharov A, Gomez B, Lyubimov A, Schwark WS, Mallicote MF, Portela DA, Bisiau AL, Wakshlag JJ.The pharmacokinetics and tolerability of cannabinoids and their metabolites were determined in eight horses after enteral administration of a commercial CBD/CBDA-rich hemp oil product. Each horse was administered 2 mg/kg or 8 mg/kg CBD/CBDA or no treatment in a randomized cross-over design. Serial serum samples collected over 48 h were analyzed by high performance liquid chromatography with tandem mass spectrometry. Plasma chemistry analysis was performed at 0 h and 24 h. Vital parameters, pedometry, and blinded mentation and gait evaluations were recorded at intervals up to 24 h. ...
Hormones and behaviorMarch 18, 2024
Volume 161 105526 doi: 10.1016/j.yhbeh.2024.105526
Granweiler J, Cristóbal-Azkarate J, Morton N, Palme R, Shultz S.In seasonal environments, maintaining a constant body temperature poses challenges for endotherms. Cold winters at high latitudes, with limited food availability, create opposing demands on metabolism: upregulation preserves body temperature but depletes energy reserves. Examining endocrine profiles, such as thyroid hormone triiodothyronine (T3) and glucocorticoids (GCs), proxies for changes in metabolic rate and acute stressors, offer insights into physiological trade-offs. We evaluated how environmental conditions and gestation impact on faecal hormone metabolites (fT3Ms and fGCMs) from late...
Luis-Calero M, Marinaro F, Fernández-Hernández P, Ortiz-Rodríguez JM, G Casado J, Pericuesta E, Gutiérrez-Adán A, González E, Azkargorta M....In vitro maturation (IVM) of oocytes is clinically used in horses to produce blastocysts but current conditions used for horses are suboptimal. We analyzed the composition of equine preovulatory follicular fluid (FF) secretome and tested its effects on meiotic competence and gene expression in oocytes subjected to IVM. Preovulatory FF was obtained, concentrated using ultrafiltration with cut-off of 10 kDa, and stored at -80 °C. The metabolic and proteomic composition was analyzed, and its ultrastructural composition was assessed by cryo-transmission microscopy. Oocytes obtained post-mortem ...
Ishii H, Ishikawa Y, Mizobe F, Nomura M, Yamanaka T, Tanabe S, Nagata SI, Yamada M, Leung GN.Osilodrostat is an inhibitor of 11-beta-hydroxylase (CYP11B) and is used for the treatment of Cushing's disease but also categorized as an anabolic agent. The use of osilodrostat is prohibited in horseracing and equestrian sports. To the best of our knowledge, this is the first metabolic study of osilodrostat in equine plasma. Methods: Potential metabolites of osilodrostat were identified by differential analysis using data acquired from pre- and post-administration plasma samples after protein precipitation with liquid chromatography electrospray ionization high-resolution mass spectrometry (...
Kruse CJ, Dieu M, Renaud B, François AC, Stern D, Demazy C, Burteau S, Boemer F, Art T, Renard P, Votion DM.Equine atypical myopathy (AM) is a severe environmental intoxication linked to the ingestion of protoxins contained in seeds and seedlings of the sycamore maple (Acer pseudoplatanus) in Europe. The toxic metabolites cause a frequently fatal rhabdomyolysis syndrome in grazing horses. Since these toxic metabolites can also be present in cograzing horses, it is still unclear as to why, in a similar environmental context, some horses show signs of AM, whereas others remain clinically healthy. Label-free proteomic analyses on the serum of 26 diseased AM, 23 cograzers, and 11 control horses were per...
Johansson L, Ringmark S, Bergquist J, Skiöldebrand E, Jansson A.The plasma metabolomic profile of elite harness horses subjected to different training programmes was explored. All horses had the same training programme from 1.5 until 2 years of age and then high-intensity training was introduced, with horses divided into high and low training groups. Morning blood samples were collected at 1.5, 2, 2.5 and 3.5 years of age. The plasma was analysed using targeted absolute quantitative analysis and a combination of tandem mass spectrometry, flow-injection analysis and liquid chromatography. Differences between the two training groups were observed at 2 yea...
Viljanto M, Love C, White D, Habershon-Butcher J, Hincks P, Gray B, Scarth J.Methandienone is an anabolic-androgenic steroid that is prohibited in equine sports due to its potential performance enhancing properties. Metabolism and detection of methandienone in equine urine have been investigated comprehensively in literature; however, there is a limited knowledge about its metabolites in equine plasma and no information about its detection in equine hair. Following a multi-dose oral administration of methandienone to two Thoroughbred horses, 17-epimethandienone, methyltestosterone, two mono-hydroxylated, two di-hydroxylated and three 17α-methylandrostanetriol metaboli...
Cutler C, Viljanto M, Taylor P, Hincks P, Habershon-Butcher J, Gray B, Scarth J.FG-4592 is a hypoxia-inducible factor inhibitor that has been approved for therapeutic use in some countries. This class of compounds can increase the oxygen carrying capacity of the blood and thus have the potential to be used as performance enhancing agents in sports. The purpose of this study was to investigate the detection of FG-4592 and metabolites in equine plasma and mane hair following a multiple dose oral administration to two Thoroughbred racehorses, to identify the best analytical targets for doping control laboratories. Urine samples were also analysed, and the results compared to...
Subhahar MB, Karakka Kal AK, Philip M, Muhammed Ajeebsanu M, Karatt TK, Perwad Z.Sickle cell disease, a debilitating genetic disorder affecting numerous newborns globally, has historically received limited attention in pharmaceutical research. However, recent years have witnessed a notable shift, with the Food and Drug Administration approving three innovative disease-modifying medications. Voxelotor, also known as GBT440, is a promising compound that effectively prevents sickling, providing a safe approach to alleviate chronic hemolytic anemia in sickle cell disease. It is a novel, orally bioavailable small molecule that inhibits hemoglobin S polymerization by enhancing o...
Taylor SD, Hart KA, Vaughn S, Giancola SC, Serpa PBS, Santos AP.Ascorbic acid (AA) is an antioxidant that might be beneficial for adjunctive treatment of sepsis in horses. The optimal dose and effects on oxidative status are unknown. Objective: Ascorbic acid administration will increase plasma AA concentrations and decrease determinants of reactive oxygen metabolites (dROM), basal and stimulant-induced intraerythrocytic reactive oxygen species (ROS) concentrations, and stimulant-induced neutrophil ROS production, and increase plasma antioxidant capacity (PAC) in a dose-dependent manner. Methods: Eight healthy horses. Methods: Randomized placebo-controlled ...
Son V, Penagos-Tabares F, Hollmann M, Khiaosa-Ard R, Sulyok M, Krska R, Zebeli Q.Pastures are used for grazing and the production of conserved roughage in horses. Yet, the nutritional profile of the forage varies from spring to late summer, affecting equine nutrient supply and health. In addition, environmental factors may also favor plant contaminants such as mycotoxins. This study aimed to determine the nutritional profile and contaminant load of selected horse pastures from early spring till late summer. The nutrient composition (main macronutrients, macro elements and trace elements), as well as mycotoxins, metabolites, pesticides, and plant-derived compounds of seven ...
Knych HK, Katzman S, McKemie DS, Arthur RM, Blea J.Lidocaine is a local anesthetic that is sometimes administered in combination with epinephrine. The addition of epinephrine increases the time lidocaine remains at the site of administration, thus prolonging the duration of effect. Due to their potential to prevent the visual detection of lameness, the administration of local anesthetics is strictly regulated in performance and racehorses. Recent reports of positive regulatory findings for lidocaine in racehorses suggests a better understanding of the behavior of this drug is warranted. The objective of the current study was to describe serum ...
Klein DJ, Anthony TG, McKeever KH.metabolomics is the high-throughput, multiparametric identification and classification of hundreds of low molecular weight metabolites in a biological sample. Ultimately, metabolites are the downstream readouts of cellular signalling, transcriptomic and proteomic changes that can provide a comprehensive view of tissue and organismal phenotype. The popularity of metabolomics in human sport and exercise has been gaining over the past decade and has provided important insights into the energetic demands and mechanistic underpinnings of exercise and training. To the contrary, metabolomics in the f...
Sander J, Cavalleri JM, Terhardt M, Bochnia M, Zeyner A, Zuraw A, Sander S, Peter M, Janzen N.Hypoglycin A (2-amino-3-(2-methylidenecyclopropyl)propanoic acid) is the plant toxin shown to cause atypical myopathy in horses. It is converted in vivo to methylenecyclopropyl acetic acid, which is transformed to a coenzyme A ester that subsequently blocks beta oxidation of fatty acids. Methylenecyclopropyl acetic acid is also conjugated with carnitine and glycine. Acute atypical myopathy may be diagnosed by quantifying the conjugates of methylenecyclopropyl acetic acid plus a selection of acyl conjugates in urine and serum. We describe a new mass spectrometric method for sample volumes of <0...
Gollnick PD, Bertocci LA, Kelso TB, Witt EH, Hodgson DR.The effect of high-intensity exercise on the respiratory capacity of skeletal muscle was studied in horses which ran five 600-m bouts on a track with 2 min of rest between exercise bouts, or once to fatigue on a treadmill at an intensity that elicited the maximal oxygen uptake. Venous blood and biopsy samples of the middle gluteal muscle were collected at rest, after each exercise bout, and 30 and 60 min post-exercise. Blood samples were analyzed for lactate concentration and pH and muscle samples for metabolites, pH, and respiratory capacity. Venous blood and muscle pH declined to 6.91 +/- 0....
Leng J, Proudman C, Darby A, Blow F, Townsend N, Miller A, Swann J.Equine grass sickness (EGS) is a frequently fatal disease of horses, responsible for the death of 1 to 2% of the U.K. horse population annually. The etiology of this disease is currently uncharacterized, although there is evidence it is associated with Clostridium botulinum neurotoxin in the gut. Prevention is currently not possible, and ileal biopsy diagnosis is invasive. The aim of this study was to characterize the fecal microbiota and biofluid metabolic profiles of EGS horses, to further understand the mechanisms underlying this disease, and to identify metabolic biomarkers to aid in diagn...
Bazzano M, Laghi L, Zhu C, Magi GE, Tesei B, Laus F.The use of an untargeted metabolomic approach to investigate biofluids of respiratory origin is of increasing interest in human and veterinary lung research. Considering the high incidence of equine asthma (> 14%) within horse population and the importance of this animal model for human disease, we aimed to investigate the metabolomic profile of bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) in healthy and asthmatic horses. Results: On the basis of clinical, endoscopic and BALF cytology findings, 6 horses with severe asthma (Group A) and 6 healthy horses (Group C) we...
Knych HK, Steffey EP, McKemie DS.The objective of the current study was to describe the pharmacokinetics of morphine and its metabolites following intravenous administration to the horse. A total of eight horses (two per dose group) received a single intravenous dose of 0.05, 0.1, 0.2, or 0.5 mg/kg morphine. Blood samples were collected up to 72 h postdrug administration, analyzed using LC-MS/MS and pharmacokinetic parameters determined. Behavior, step counts, and gastrointestinal activity were also assessed. The beta and gamma half-life for morphine ranged from 0.675 to 2.09 and 6.70 to 18.1 h, respectively, following admini...
Ji Z, Zhang J, Deng C, Hu Z, Du Q, Guo T, Wang J, Fan R, Han R, Yang Y.Mare milk(MM)production is lower than that of cow milk (CM), making it a premium product. Unfortunately, sellers adulterate MM with cheap CM to unscrupulously gain more profits. This study aimed to analyze MM adulteration with CM using proteomics and metabolomics. Using univariate and multivariate statistical analysis, the relative abundances of certain proteins of caseins and secretoglobin family 1D member were found to be higher with a higher CM admixture percentage. In addition, several metabolites, such as orotic and 4-aminonicotinic acids, increased in the mare-cow milk mixture with an in...
Fernández-Hernández P, Sánchez-Calabuig MJ, García-Marín LJ, Bragado MJ, Gutiérrez-Adán A, Millet Ó, Bruzzone C, González-Fernández L....Production of equine embryos in vitro is currently a commercial technique and a reliable way of obtaining offspring. In order to produce those embryos, immature oocytes are retrieved from postmortem ovaries or live mares by ovum pick-up (OPU), matured in vitro (IVM), fertilized by intracytoplasmic sperm injection (ICSI), and cultured until day 8-10 of development. However, at best, roughly 10% of the oocytes matured in vitro and followed by ICSI end up in successful pregnancy and foaling, and this could be due to suboptimal IVM conditions. Hence, in the present work, we aimed to elucidate the ...
McGowan CM, Golland LC, Evans DL, Hodgson DR, Rose RJ.Thirteen Standardbred horses trained intensively for 34 weeks and detrained for 12 weeks to investigate the effects of training, overtraining and detraining on muscle metabolites, buffering capacity and enzyme activities (CS, HAD and LDH). After a standardised exercise test to fatigue at 10 m/s (approximately 100% VO2max), there was significant depletion of [ATP], [PCr] and muscle [glycogen] and accumulation of muscle and plasma [lactate], [NH3] and elevated muscle temperature. After training, associated with increased run time to fatigue (148%), there was reduced depletion of muscle [glycogen...
Delarocque J, Frers F, Feige K, Huber K, Jung K, Warnken T.Little is known about the implications of hyperinsulinemia on energy metabolism, and such knowledge might help understand the pathophysiology of insulin dysregulation. Objective: Describe differences in the metabolic response to an oral glucose test, depending on the magnitude of the insulin response. Methods: Twelve Icelandic horses in various metabolic states. Methods: Horses were subjected to 3 oral glucose tests (OGT; 0.5 g/kg body weight glucose). Basal, 120 and 180 minutes samples were analyzed using a combined liquid chromatography tandem mass spectrometry and flow injection analysis ...
Knych HK, Baden RW, Gretler SR, McKemie DS.Despite their widespread popularity as sport and companion animals and published and anecdotal reports of vast difference in drug disposition and pharmacokinetics between individuals, studies describing equine drug metabolism are limited. It has been theorized that similar to humans, members of the CYP2D family in horses may be polymorphic in nature leading to differences in metabolism of substrates. This study aims to build on the limited current knowledge regarding P450 mediated metabolism in horses by describing the metabolism of the polymorphic CYP2D6 probe drug codeine in vitro. Codeine, ...
Rose RJ, Hodgson DR, Kelso TB, McCutcheon LJ, Reid TA, Bayly WM, Gollnick PD.This study determined maximal O2 uptake (VO2max), maximal O2 deficit, and O2 debt in the Thoroughbred racehorse exercising on an inclined treadmill. In eight horses the O2 uptake (VO2) vs. speed relationship was linear until 10 m/s and VO2max values ranged from 131 to 153 ml.kg-1.min-1. Six of these horses then exercised at 120% of their VO2max until exhaustion. VO2, CO2 production (VCO2), and plasma lactate (La) were measured before and during exercise and through 60 min of recovery. Muscle biopsies were collected before and at 0.25, 0.5, 1, 1.5, 2, 5, 10, 15, 20, 40, and 60 min after exercis...
Tobin T, Chay S, Kamerling S, Woods WE, Weckman TJ, Blake JW, Lees P.Phenylbutazone is an acidic, lipophilic, non-steroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, gamma-hydroxyoxyphenbutazone, account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE2. It appears to act on prostaglandin-H synthase and pros...
Deng L, Yang Y, Li Z, Li J, Zhu Y, Meng Q, Liu J, Wang X.Despite mare's milk being highly nutritious and beneficial to human health, the effects of different dietary regimens on the lipid profile of mare's milk remain to be completely understood. Herein we employed targeted multiple reaction monitoring-based lipidomics with ultra-high performance liquid chromatography-quadrupole time-of-flight-mass spectrometry to compare the milk lipid profiles of mares fed: pasture grass (P), corn stover and concentrate (H), or cornsilage and concentrate (S). Overall, 461 lipids belonging to 17 subclasses were identified; 261 significantly different lipids were id...
Paßlack N, Vahjen W, Zentek J.Cellobiose is a disaccharide with potential prebiotic effects, as demonstrated in different animal species, but not yet in horses. It was, therefore, the aim of the present study to evaluate the impact of dietary cellobiose on the fecal microbiota of horses. Eight healthy adult horses and two ponies were included in this study. The animals received a diet without or with 10 g and 20 g cellobiose per day for 14 days each. At the end of the feeding periods, fresh fecal samples were collected to measure bacterial metabolites and the microbial composition. For the microbiota analysis, 16S rRNA ...
Satué K, Fazio E, Ferlazzo A, Medica P.The aim of this study was to verify the existence of possible cross-talk between biochemical contents of follicular fluid (FF) and systemic concentrations according to the follicular development of the metabolites: glucose (GLU), lactate (LACT), cholesterol (CHOL), triglycerides (TG), total bilirubin (T BIL), blood urea nitrogen (BUN), and creatinine (CREAT); enzymatic activities: gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and aspartate aminotransferase (AST); electrolytes: calcium (Ca), phosphorus (P), sodium (Na), chloride (Cl), potassium (K), ...
Songsermsakul P, Böhm J, Aurich C, Zentek J, Razzazi-Fazeli E.Concentration profile of zearalenone (ZON) and its metabolites in plasma, urine and faeces samples of horses fed with Fusarium toxin-contaminated oats is described. In plasma, β-zearalenol (β-ZOL) was detected at high levels on day 10 of the study (3.21-6.24 μg/l). β-Zearalenol and α-zearalenol were the major metabolites in urine. Zearalenone, α-ZOL and β-ZOL were predominantly found in faeces. Zearalanone could also be detected in urine (1.34-5.79 μg/l) and faeces (1 μg/kg). The degree of glucuronidation was established in all sample types, approximately 100% in urine and plasm...
Guan F, Uboh C, Soma L, Hess A, Luo Y, Tsang DS.Beclomethasone dipropionate (BDP) is a potent pro-drug to beclomethasone (BOH) and is used in the treatment of chronic and acute respiratory disorders in the horse. The therapeutic dose of BDP (325 microg per horse) by inhalation results in very low plasma and urinary concentrations of BDP and its metabolites that pose a challenge to detection and confirmation by equine forensic laboratories. To solve this problem, a method involving the use of a liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) was developed for the detection, confirmation and quantification of the analyt...
Miglio A, Maslanka M, Di Tommaso M, Rocconi F, Nemkov T, Buehler PW, Antognoni MT, Spitalnik SL, D'Alessandro A.The use of omics technologies in human transfusion medicine has improved our understanding of the red blood cell (RBC) storage lesion(s). Despite significant progress towards understanding the storage lesion(s) of human RBCs, a comparison of basal and post-storage RBC metabolism across multiple species using omics technologies has not yet been reported, and is the focus of this study. Blood was collected in a standard bag system (CPD-SAG-Mannitol) from dogs (n=8), horses, bovines, and donkeys (n=6). All bags were stored at 4°C for up to 42 days (i.e., the end of the shelf life in Italian vete...
Scarth JP, Teale P, Kuuranne T.A detailed understanding of equine drug metabolism is important for detection of drug abuse in horseracing and also in veterinary drug development and practice. To date, however, no comprehensive review of equine drug metabolism has been published. The majority of literature regarding equine drug metabolite profiles is derived from sports drug detection research and is generally targeted at detecting marker metabolites of drug abuse. However, the bulk of the literature on equine drug metabolism enzymology is derived from veterinary studies aimed at determining the molecular basis of metabolism...
Letendre LT, Tessman RK, McClure SR, Kvaternick VJ, Fischer JB, Hanson PD.To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. Methods: 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. Methods: In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma ...
Silver M, Fowden AL, Knox J, Ousey JC, Franco R, Rossdale PD.The effects of insulin-induced hypoglycaemia on plasma catecholamines, cortisol and metabolites have been examined in newborn and 7-14-day-old foals. The fall in plasma glucose elicited by the highest dose of insulin (1.0 i.u./kg) given to the neonates was slower in onset and less severe in effect than 0.5 i.u./kg in the older foals. There was a significant inverse correlation between the concentrations of glucose and adrenaline (but not noradrenaline) in plasma once the glucose level had fallen below 2 mmol/l; the adrenergic response to hypoglycaemia was greater in the 7-14-day-old foals than...
Shilo Y, Britzi M, Eytan B, Lifschitz T, Soback S, Steinman A.Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were ...
Ho EN, Leung DK, Leung GN, Wan TS, Wong AS, Wong CH, Soma LR, Rudy JA, Uboh C, Sams R.Administration studies of levamisole in horses were carried out using two different levamisole preparations, namely, levamisole hydrochloride oral bolus and levamisole phosphate injectable solution. These preparations were analysed in detail for the presence of aminorex-like impurities. Both levamisole preparations were found to contain 1-(2-mercaptoethyl)-4-phenyl-2-imidazolidinone (I) and 4-phenyl-2-imidazolidinone (II) as degradation impurities, but neither aminorex nor rexamino was detected in these preparations. After the administration of these preparations to horses, aminorex, rexamino,...
Liu Y, Siard M, Adams A, Keowen ML, Miller TK, Garza F, Andrews FM, Seeram NP.The human health benefits attributed to turmeric/curcumin spice has resulted in its wide utilization as a dietary supplement for companion pets and other animals including horses. While the quantification of free curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and their phase-2 metabolites (curcumin-O-sulfate, curcumin-O-glucuronide) have been extensively investigated in human and rodent biological samples (primarily plasma and serum), there is lack of similar data for horses. Herein, we report a validated LC-ESI-MS/MS method for the simultaneous quantification of the aforemen...
Laus F, Gialletti R, Bazzano M, Laghi L, Dini F, Marchegiani A.Osteoarthritis (OA) is a common cause of lameness in sport horses with a significant economic impact. The prevention of OA is crucial since no effective treatment is available. This study aimed to apply untargeted metabolomic analysis to investigate the differences in synovial fluid (SF) composition between healthy and OA-affected joints in horses. SF collected from healthy (n.8) and OA (n.11) horses was analyzed using H-NMR analysis. Metabolomic analysis allowed 55 different metabolites to be identified and quantified in SF samples. Nineteen metabolites were found to be differently concentrat...
Lankveld DP, Driessen B, Soma LR, Moate PJ, Rudy J, Uboh CE, van Dijk P, Hellebrekers LJ.Ketamine (KET) possesses analgesic and anti-inflammatory activity at sub-anesthetic doses, suggesting a benefit of long-term KET treatment in horses suffering from pain, inflammatory tissue injury and/or endotoxemia. However, data describing the pharmacodynamic effects and safety of constant rate infusion (CRI) of KET and its pharmacokinetic profile in nonpremedicated horses are missing. Therefore, we administered to six healthy horses a CRI of 1.5 mg/kg/h KET over 320 min following initial drug loading. Cardiopulmonary parameters, arterial blood gases, glucose, lactate, cortisol, insulin, non...
Chou CC, Vickroy TW.To determine the presence of adenosine receptor subtypes A1 and A2a in equine forebrain tissues and to characterize the interactions of caffeine and its metabolites with adenosine receptors in the CNS of horses. Methods: Brain tissue specimens obtained during necropsy from 5 adult male research horses. Methods: Membrane-enriched homogenates from cerebral cortex and striatum were evaluated by radioligand binding assays with the A1-selective ligand [3H]DPCPX and the A2a-selective ligand [3H]ZM241385. Functional responses to adenosine receptor agonists and antagonists were determined by a nucleot...
Steelman SM, Johnson P, Jackson A, Schulze J, Chowdhary BP.Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of...
Shepherd ML, Ponder MA, Burk AO, Milton SC, Swecker WS.The purpose of the present study was to compare digestibility of grass hay, faecal and plasma volatile fatty acid (VFA) concentrations, and faecal bacterial abundance in overweight and moderate-condition mares. Five overweight adult mixed-breed mares and five adult mixed-breed mares in moderate condition were housed individually and limit-fed orchard grass (Dactylis glomerata) hay at 20 g/kg body weight (as fed) daily for 14 d. Forage DM and fibre digestibility were determined using AOAC methods; digestible energy was measured using bomb calorimetry; plasma and faecal VFA concentrations were ...
