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.
Tueshaus T, McKemie DS, Kanarr K, Kass PH, Knych HK.Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus aceta...
Karatt TK, Sathiq MA, Laya S, Kal AKK, Subhahar MB, Muhammed Ajeebsanu MP, Philip M, Caveney MR, Graiban FM.Nonsteroidal selective androgen receptor modulators (SARMs) are a novel class of compounds that have not yet been clinically approved; however, they appear to have a better anabolic/androgenic ratio than steroids and cause slighter side effects. Sports drug testing laboratories are required to maintain continuously updated doping control analytical methods in light of the widespread misuse of SARMs in elite and amateur sports. This paper describes the metabolic conversion of SARM GSK2881078 in thoroughbred horses following oral administration and in vitro with equine liver microsomes. A liquid...
Poth MKM, McKemie DS, Traynham M, Kass PH, Knych HK.The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6-glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a...
Keen B, Cawley A, Reedy B, Noble G, Loy J, Fu S.The use of catechol-O-methyltransferase inhibitors may mask doping agents, primarily levodopa, administered to racehorses and prolong the stimulating effects of dopaminergic compounds such as dopamine. It is known that 3-methoxytyramine is a metabolite of dopamine and 3-methoxytyrosine is a metabolite of levodopa thus these compounds are proposed to be potential biomarkers of interest. Previous research established a urinary threshold of 4,000 ng/mL for 3-methoxytyramine to monitor misuse of dopaminergic agents. However, there is no equivalent biomarker in plasma. To address this deficiency a...
Weinert-Nelson JR, Biddle AS, Sampath H, Williams CA.Integrating warm-season grasses into cool-season equine grazing systems can increase pasture availability during summer months. The objective of this study was to evaluate effects of this management strategy on the fecal microbiome and relationships between fecal microbiota, forage nutrients, and metabolic responses of grazing horses. Fecal samples were collected from 8 mares after grazing cool-season pasture in spring, warm-season pasture in summer, and cool-season pasture in fall as well as after adaptation to standardized hay diets prior to spring grazing and at the end of the grazing seaso...
Karatt TK, Sathiq MA, Laya S, Philip M, Karakka Kal AK, Subhahar MB.An effective alternative to testosterone therapy is selective androgen receptor modulators, a class of compounds that has a tissue-specific effect on muscle and bone. These drugs, which enhance performance, pose a severe abuse risk in competitive sports. GLPG0492 is one of the selective androgen receptor modulators discovered in recent decades. This compound has a unique tissue-specific action for muscle and bone against steroid receptors and acts as a partial agonist for androgen receptors. This study examined GLPG0492 and its metabolites in vitro using equine liver microsomes. Liquid chromat...
Karatt TK, Sathiq MA, Laya S, Karakka Kal AK, Subhahar MB, M P MA, Philip M, Graiban FM, Caveney MR.Since 2010, there has been an increasing number of adverse analytical findings related to selective androgen receptor modulators (SARMs) in competitive sports. It emphasizes the importance of comprehensive doping control analytical procedures that are capable of detecting SARM misuse. Methods: In this study, it is described how LY2452473, a SARM, was metabolized in thoroughbred horses after a single-dose oral administration and in vitro with equine liver microsome preparations. An investigation of the metabolism of LY2452473 in horses' urine, plasma, and hair matrices was carried out during th...
MacNicol JL, Renwick S, Ganobis CM, Allen-Vercoe E, Weese JS, Pearson W.The microbes that reside within the equine hindgut create a complex and dynamic ecosystem. The equine hindgut microbiota is intimately associated with health and, as such, represents an area which can be beneficially modified. Synbiotics, supplements that combine probiotic micro-organisms with prebiotic ingredients, are a potential means of influencing the hindgut microbiota to promote health and prevent disease. The objective of the current study was to evaluate the influence of an equine probiotic/prebiotic supplement on characteristics of the microbiota and metabolite production in vitro. E...
Staniszewska M, Kowalik S, Sadok I, Kędzierski W.Catabolism of tryptophan (Trp) is modulated by physical activity and provides a pool of active compounds: Trp is considered a calmative agent, kynurenine (Kyn) and 3-hydroxykynurenine (3-HKyn) show neurotoxic effects, kynurenic acid (Kyna) and xanthurenic acid (XA) have neuroprotective properties like nicotinamide (NAm), while serotonin is the neurotransmitter. The study was conducted to investigate the dependence of exercise intensity, measured by plasma lactic acid (LA) concentration, on the level of Trp, its catabolites (serotonin, Kyn, 3-HKyn, Kyna and XA), and NAm in Thoroughbred horses. ...
Delank K, Reese S, Erhard M, Wöhr AC.This study had the aim to demonstrate the midterm effects (three weeks) of weaning on foals' welfare. For this purpose, foals' behavioral changes and fecal levels metabolites of cortisol were evaluated. The observations took place at the state stud farm of Baden-Wuerttemberg in Germany. Ten foals (six colts and four fillies) were observed from one day before weaning up until three weeks after weaning. Weaning was divided into three blocks, the first in September, the second in October, and the last in November. The behavioral observation was done during an eight-hour period between 7:00 a.m. a...
Harding C, Viljanto M, Habershon-Butcher J, Taylor P, Scarth J.YK-11 is a steroidal selective androgen receptor modulator, a compound class prohibited in both equine racing and human sports because of their potentially performance enhancing properties. YK-11 is easily accessible via internet-based supplement vendors making this compound a possible candidate for doping; however, its phases I and II metabolism has not yet been reported in the horse. The purpose of this study was to investigate the in vivo metabolites of YK-11 in urine and plasma following oral administration with three daily doses of 50 mg to two Thoroughbred horses. In vitro incubations ...
Wang T, Zeng Y, Ma C, Meng J, Wang J, Ren W, Wang C, Yuan X, Yang X, Yao X.In this study, the plasma non-targeted metabolomics of Yili horses were characterized before and after exercise on tracks that differed in surface hardness to better understand exercise-related biochemical changes. Blood samples were obtained from eight trained Yili horses before and immediately after exercise. Samples were used for metabolomic analysis by ultra-performance liquid chromatography-Q-EXACTIVE mass spectrometry. In total, 938 significantly different metabolites involving sugar, lipid, and amino acid metabolism were detected in the plasma, with significant increases in glucose, glu...
Kabil E, Göktaş EF, Güneş E, Yatanaslan L, Zor TA, Tektaş MH, İnceman B, Tufan M.A recent trend in the use of high-resolution accurate mass screening (HRAMS) for doping control testing in both human and animal sports has emerged owing to significant improvement in high-resolution mass spectrometry in terms of sensitivity, mass accuracy, mass resolution and mass stability. Several HRAMS methods have been reported for the detection of multidrug residues in human or equine urine. These improved analytical technologies have led to changes in the use of prohibited substances, and the administration of more than one substance at low concentrations as a "cocktail" has become one ...
Sandbaumhüter FA, Aerts JT, Theurillat R, Andrén PE, Thormann W, Jansson ET.The chiral drug ketamine has long-lasting antidepressant effects with a fast onset and is also suitable to treat patients with therapy-resistant depression. The metabolite hydroxynorketamine (HNK) plays an important role in the antidepressant mechanism of action. Hydroxylation at the cyclohexanone ring occurs at positions 4, 5, and 6 and produces a total of 12 stereoisomers. Among those, the four 6HNK stereoisomers have the strongest antidepressant effects. Capillary electrophoresis with highly sulfated γ-cyclodextrin (CD) as a chiral selector in combination with mass spectrometry (MS) was us...
Taguchi T, Morales Yniguez FJ, Takawira C, Andrews FM, Lopez MJ.Osteoarthritis (OA) accounts for up to 60% of equine lameness. Agmatine, a decarboxylated arginine, may be a viable option for OA management, based on reports of its analgesic properties. Six adult thoroughbred horses, with lameness attributable to thoracic limb OA, received either daily oral phenylbutazone (6.6 mg/kg), agmatine sulfate (25 mg/kg) or a control for 30 days, with 21-day washout periods between treatments. Subjective lameness, thoracic limb ground reaction forces (GRF), plasma agmatine and agmatine metabolite levels were evaluated using an established rubric, a force platform, an...
Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Mathew B, Perwad Z, Graiban FM, Caveney MR, Sayed R, Kadry AM.According to previous research, aminorex is the major metabolite of levamisole; however, in the screening of levamisole-positive racehorse urine and plasma samples, aminorex could only be detected in trace amounts or not at all. In forensic laboratories, hydroxy levamisole and its phase II conjugates make it easier to confirm levamisole misuse and to differentiate between the abuse of levamisole and aminorex. This study aimed to identify the major levamisole metabolites that can be detected along with the parent drug. Methods: The study describes levamisole and its metabolites in thoroughbred ...
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...
Adler DMT, Jørgensen E, Cornett C.To determine the synovial fluid (SF) concentrations of lidocaine and mepivacaine after intra-articular injection with clinically relevant doses to the distal interphalangeal (DIP), metacarpophalangeal (MCP), middle carpal (MC), and tarsocrural (TC) joint at two different time points after injection in order to be able to compare concentrations with previously established concentrations associated with cytotoxicity and antimicrobial activity. Unassigned: In the first of two experiments, 20 joints (5 MC, 5 MCP, 10 DIP joints) of five horses under general anesthesia were injected with clinically ...
Sanclemente JL, Rivera-Velez SM, Horohov DW, Dasgupta N, Sanz MG.Foals that develop pulmonary ultrasonographic lesions on Rhodococcus equi (R. equi) endemic farms are treated with antibiotics because those at risk of developing clinical pneumonia (~20%) cannot be recognised early. Candidate biomarkers identified using metabolomics may aid targeted treatment strategies against R. equi. Objective: (1) To describe how foal ageing affects their plasma metabolome (birth to 8 weeks) and (2) to establish the effects that experimental infection with Rhodococcus equi (R. equi) has on foal metabolome. Methods: Experimental study. Methods: Nine healthy newborn foals...
Catalán J, Martínez-Rodero I, Yánez-Ortiz I, Mateo-Otero Y, Bragulat AF, Nolis P, Carluccio A, Yeste M, Miró J.Follicular fluid is formed from the transudation of theca and granulosa cells in the growing follicular antrum. Its main function is to provide an optimal intrafollicular microenvironment to modulate oocyte maturation. The aim of this study was to determine the metabolomic profile of preovulatory follicular fluid (PFF) in jennies. For this purpose, PFF was collected from 10 follicles of five jennies in heat. Then, PFF samples were analysed by nuclear magnetic resonance (NMR) and heteronuclear single quantum correlation (2D H/C HSQC). Our study revealed the presence of at least 27 metabolites i...
Bazzano M, Zhu C, Laus F, Giambattista AD, Laghi L.The application of the 'omics' studies in the field of animal reproduction has been aimed at identifying novel biomarkers of fertility since the last few years. When assessing reproductive efficiency in horses, breed should also be taken into account as it can influence semen quality and fertility. Considering the growing interest in metabolomic analysis to evaluate male fertility, we aimed to investigate the metabolomic profile of seminal plasma in two different horse breeds. Twelve healthy stallions, n.6 American Quarter Horse (AQH) and n.6 Italian Draft Horse (IDH) stallions, regularly used...
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN.In drug metabolism studies in horses, non-targeted analysis by means of liquid chromatography coupled with high-resolution mass spectrometry with data-dependent acquisition (DDA) has recently become increasingly popular for rapid identification of potential biomarkers in post-administration biological samples. However, the most commonly encountered problem is the presence of highly abundant interfering components that co-elute with the target substances, especially if the concentrations of these substances are relatively low. In this study, we evaluated the possibility of expanding DDA coverag...
Main SC, Brown LP, Melvin KR, Campagna SR, Voy BH, Castro HF, Strickland LG, Hines MT, Jacobs RD, Gordon ME, Ivey JLZ.The large population of emaciated horses continues to be an issue troubling the equine industry. However, little is known regarding the collection of equine metabolites (metabolome) during a malnourished state and the changes that occur throughout nutritional rehabilitation. In this study, ten emaciated horses underwent a refeeding process, during which blood samples were collected for a blood chemistry panel and metabolomics analysis via ultrahigh performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Significant differences among blood chemistry analytes and metabo...
Jahn P, Dobešová D, Brumarová R, Tóthová K, Kopecká A, Friedecký D.Equine atypical myopathy (AM also referred to as multiple acyl-CoA dehydrogenases deficiency [MADD]) is thought to be caused by toxins metabolized from hypoglycin A (HGA) and méthylènecyclopropylglycine (MCPrG). HGA is contained in the seeds and seedlings of the sycamore tree (Acer pseudoplatanus); MCPrG has so far only been confirmed in seeds. Among other things, these substances can disrupt the fatty acids β-oxidation pathway with the subsequent accumulation of certain acylcarnitines. The tentative diagnosis is based on anamnesis and clinical signs and can be verified by the detection of ...
Ishii H, Shibuya M, Leung GN, Yamashita S, Nagata SI, Kushiro A, Sakai S, Toju K, Okada J, Kawasaki K, Kusano K, Kijima-Suda I.For the purpose of doping control, this is the first report of accurate quantification of four critical structural isomers of nicotine metabolites (trans-3'-hydroxycotinine, cis-3'-hydroxycotinine, 5'-hydroxycotinine, and N'-hydroxymethylnorcotinine) in equine plasma and urine for the establishment of their elimination profiles. Besides, the pharmacokinetic studies of trans-3'-hydroxycotinine and N'-hydroxymethylnorcotinine in equine plasma and urine are also presented for the first time. Methods: The accurate quantification methods of the aforementioned four structural isomers in horse plasma...
Current drug metabolismAugust 27, 2022
Volume 23, Issue 10 850-865 doi: 10.2174/1389200223666220825093945
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN.Vadadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, is a substance which carries a lifetime ban in both horse racing and equestrian competition. A comprehensive metabolic study of vadadustat in horses has not been previously reported. Objective: Metabolism and elimination profiles of vadadustat in equine plasma and urine were studied for the purpose of doping control. Methods: A nasoesophageal administration of vadadustat (3 g/day for 3 days) was conducted on three thoroughbred mares. Potential metabolites were comprehensively detected by differential analysis of ful...
MacNicol JL, Renwick S, Ganobis CM, Allen-Vercoe E, Weese JS, Pearson W.The equine gastrointestinal (GI) microbiota is intimately related to the horse. The objective of the current study was to evaluate the microbiome and metabolome of cecal inoculum maintained in an anaerobic chamber or chemostat batch fermenter, as well as the fecal slurry maintained in an anaerobic chamber over 48 h. Cecal and fecal content were collected from healthy adult horses immediately upon death. Cecal fluid was used to inoculate chemostat vessels (chemostat cecal, = 11) and vessels containing cecal fluid (anaerobic cecal, = 15) or 5% fecal slurry (anaerobic fecal, = 6) were maintain...
Burroughs DL, Lorch G, Guo Y, Hill K, Schroeder EL, Cole LK, Phelps MA.Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA) which acts as an immunosuppressive agent. During the biotransformation of MMF to MPA, additional metabolites including MPA phenol glucuronide (MPAG), MPA acyl glucuronide (AcMPAG) and MPA phenol glucoside (MPG) are formed. Objective: To define the noncompartmental pharmacokinetic (PK) parameters of three single doses of intravenous (i.v.) MMF and its downstream metabolites in healthy horses. Methods: Six healthy Standardbred mares. Methods: Generic MMF (Par Pharmaceuticals; Chestnut Ridge, NY, USA) was reconstituted and admi...
Park JW, Kim KH, Kim S, So JR, Cho BW, Song KD.The integration of metabolomics and transcriptomics may elucidate the correlation between the genotypic and phenotypic patterns in organisms. In equine physiology, various metabolite levels vary during exercise, which may be correlated with a modified gene expression pattern of related genes. Integrated metabolomic and transcriptomic studies in horses have not been conducted to date. The objective of this study was to detect the effect of moderate exercise on the metabolomic and transcriptomic levels in horses. In this study, using nuclear magnetic resonance (NMR) spectroscopy, we analyzed the...
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...
Frank N, Elliott SB, Chameroy KA, Tóth F, Chumbler NS, McClamroch R.Pituitary pars intermedia dysfunction (PPID) is a risk factor for pasture-associated laminitis, which follows a seasonal pattern. Objective: Hormonal responses to season differ between PPID and unaffected horses. Methods: Seventeen horses aged 8-30 years (14 horses ≥ 20 years of age). Methods: Longitudinal observational study. Blood was collected monthly from August 2007 until July 2008 after pasture grazing and again after overnight stall confinement. Blood hormone and metabolite concentrations were measured and pasture grass samples were analyzed to determine carbohydrate content. Analysis...
Anderson JR, Phelan MM, Clegg PD, Peffers MJ, Rubio-Martinez LM.Osteoarthritis (OA), osteochondrosis (OC), and synovial sepsis in horses cause loss of function and pain. Reliable biomarkers are required to achieve accurate and rapid diagnosis, with synovial fluid (SF) holding a unique source of biochemical information. Nuclear magnetic resonance (NMR) spectroscopy allows global metabolite analysis of a small volume of SF, with minimal sample preprocessing using a noninvasive and nondestructive method. Equine SF metabolic profiles from both nonseptic joints (OA and OC) and septic joints were analyzed using 1D H NMR spectroscopy. Univariate and multivariate ...
Kvaternick V, Pollmeier M, Fischer J, Hanson PD.The primary objective of this study was to determine the pharmacokinetic profile of firocoxib, a novel second generation coxib, in horses. Horses were administered either a single oral or intravenous dose of firocoxib at 0.1 mg/kg in a two-period crossover study with 12 animals. The dosage was based on previously determined pharmacodynamic parameters. Oral firocoxib was well absorbed with an average bioavailability (absolute) of 79% and a Cmax of 75 ng/mL at 3.9 h. The average elimination half-life was 30 h. Following intravenous administration the average Cmax was 210 ng/mL and the eliminatio...
The attention of sports community toward probiotic supplementation as a way to promote exercise and training performance, together with good health, has increased in recent years. This has applied also to horses, with promising results. Here, for the first time, we tested a probiotic mix of several strains of live bacteria typically employed for humans to improve the training performance of Standardbred horses in athletic activity. To evaluate its effects on the horse performance, we measured lactate concentration in blood, a translational outcome largely employed for the purpose, combined wit...
Bazzano M, Laghi L, Zhu C, Magi GE, Serri E, Spaterna A, Tesei B, Laus F.The present work characterized the metabolomic profile of tracheal wash (TW) and exhaled breath condensate (EBC) in healthy horses and horses with respiratory disease. Six asthma-affected horses (group A) and six healthy controls (group H) underwent clinical, endoscopic and cytologic examinations of upper airways to confirm the active phase of asthma. TW and EBC samples were collected from each animal and investigated by proton nuclear magnetic resonance (H-NMR) metabolomic analysis. A total of ten out of 38 metabolites found in the TW were significantly different between the groups (p < ...
Songsermsakul P, Sontag G, Cichna-Markl M, Zentek J, Razzazi-Fazeli E.The paper describes a method for the sensitive and selective determination of zearalenone and its metabolites in urine, plasma and faeces of horses by high performance liquid chromatography and atmospheric pressure chemical ionisation (APCI) mass spectrometry (MS). While only one step sample clean-up by an immunoaffinity column (IAC) was sufficient for plasma samples, urine and faeces samples had to be prepared by a combination of a solid-phase extraction (SPE) and an immunoaffinity column. The method allows the simultaneous determination of zearalenone and all of its metabolites; alpha-zearal...
Le Moyec L, Robert C, Triba MN, Billat VL, Mata X, Schibler L, Barrey E.During long distance endurance races, horses undergo high physiological and metabolic stresses. The adaptation processes involve the modulation of the energetic pathways in order to meet the energy demand. The aims were to evaluate the effects of long endurance exercise on the plasma metabolomic profiles and to investigate the relationships with the individual horse performances. The metabolomic profiles of the horses were analyzed using the non-dedicated methodology, NMR spectroscopy and statistical multivariate analysis. The advantage of this method is to investigate several metabolomic path...
Zhu C, Faillace V, Laus F, Bazzano M, Laghi L.Metabolomics has been recognized as a powerful approach for disease screening. In order to highlight potential health issues in subjects, a key factor is the possibility to compare quantitatively the metabolome of their biofluids with reference values from healthy individuals. Such efforts towards the systematic characterization of the metabolome of biofluids in perfect health conditions, far from concluded for humans, have barely begun on horses. The present work attempts, for the first time, to give reference quantitative values for the molecules mostly represented in the urine metabolome of...
Neirinckx E, Vervaet C, De Boever S, Remon JP, Gommeren K, Daminet S, De Backer P, Croubels S.Species differences in oral bioavailability, first-pass metabolism and pharmacokinetics of biopharmaceutics classification system (BCS) class I compound acetaminophen were studied. The absolute bioavailability was 42.2%, 39.0%, 44.5%, 75.5% and 91.0% in chickens, turkeys, dogs, pigs and horses, respectively. After hydrolysis of metabolites by beta-glucuronidase/sulfatase, apparent bioavailability increased significantly in all species (turkeys: 72.4%, dogs: 100.5%, pigs: 102.2%), except horses (91.6%). Mean metabolic ratios of [acetaminophen glucuronide]/[acetaminophen] between 0 and 1h were s...
Orth MW, Peters TL, Hawkins JN.Glucosamine and chondroitin sulphate in many animal and human trials has improved joint health. In vitro studies are beginning to clarify their mode of action. The objective of this research was to: 1) determine at what concentrations glucosamine-HCl (GLN) and/or chondroitin sulphate (CS) would inhibit the cytokine-induced catabolic response in equine articular cartilage explants and 2) to determine if a combination of the 2 was more effective at inhibiting the catabolic response than the individual compounds. Articular cartilage was obtained from carpal joints of horses (age 1-4 years). Carti...
Baker H, DeAngelis B, Frank O.Many cell culture media use different sera to enhance growth. We assayed vitamins and some related metabolites in different sera and identified the concentration of: thiamin, biotin, folates, riboflavin, pantothenates, nicotinates, vitamins B6, B12, A, E, C, and carotenes and some related metabolites: biopterins, free inositol, free and total choline, total carnitines in chicken, horse, rabbit, goat, pig, calf, newborn calf, fetal calf and human sera. Results indicate that vitamin and metabolite content of different sera vary. Such variations could produce fluctuant effects on cell culturings ...
Hamamoto-Hardman BD, Steffey EP, Weiner D, McKemie DS, Kass P, Knych HK.The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total prote...
Li N, Xie Q, Chen Q, Evivie SE, Liu D, Dong J, Huo G, Li B.Studies on the possible alternative supplements to breastmilk are gaining research interests. Although milk from cow, goat, and mare is nutritious, its effects on the relationship between the immune system, metabolites, and gut microbiota remain unclear. This study aimed to comprehensively evaluate the effects of cow, goat, and mare milk on the immune system, metabolites, and gut microbiota of mice colonized by healthy infant feces using human milk as a standard. We examined the serum biochemistry parameters, immunity indicators, T cells, gut microbiota abundance, and metabolites. Results show...
Kenéz Á, Warnken T, Feige K, Huber K.Insulin dysregulation in horses is a metabolic condition defined by high insulin concentrations in the blood and peripheral insulin resistance. This hyperinsulinemia is often associated with severe damage in the hooves, resulting in laminitis. However, we currently lack detailed information regarding the potential involvement of particular metabolic pathways in pathophysiological causes and consequences of equine insulin dysregulation. This study aimed to assess the dynamic metabolic responses given to an oral glucose test (OGT) in insulin-sensitive and insulin-dysregulated horses by a targete...
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 ...
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...
