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.
Tsopp E, Kilk K, Gambini A, Tvrdà E, Viljaste-Seera A, Tuppits U, Jaakma Ü.Equine in vitro embryo production (IVP) via ovum pick-up (OPU) and intracytoplasmic sperm injection (ICSI) has gained prominence in sport-horse breeding due to high success rates, efficient semen utilization, and year-round embryo production, including from mares with fertility challenges or postmortem. However, assessing viability of early-stage ICSI-produced equine embryos remains challenging due to subjective morphological evaluations and limited visibility of developmental features. Non-invasive metabolomic analysis of culture media offers a promising alternative to enhance embryo selectio...
Vasco ACCM, Warren LK, Silva GM, Cuervo-Vivas W, Brandi RA, Silva VP, Lance JM, Dubeux JC, Wickens CL.Rhizoma peanut (RP, Arachis glabrata Benth) is an alternative legume forage to alfalfa (ALF, Medicago sativa L.) with less non-structural carbohydrates and crude protein. Yet, metabolic responses to consuming RP hay have never been evaluated in horses. Objective: The objective of this study was to investigate the effect of feeding RP 'Florigraze' hay on fecal and blood metabolic variables compared to alfalfa 'Legendary XHD' and bermudagrass (BMG, Cynodon dactylon L. 'Coastal') hays fed to maintenance horses. Methods: Six mature Quarter Horse geldings (596±40 kg) were randomly assigned to one ...
Satué K, Fazio E, Velasco-Martínez MG, Barbiera G, La Fauci D.Growth hormone (GH) influences follicular development mainly by stimulating insulin-like growth factor 1 (IGF-1), which acts systemically and locally within the ovary. However, the metabolic profile of follicular fluid (FF) in mares, particularly markers such as fructosamine (FRUCT), an indicator of glucose metabolism, remains poorly characterized. This study aimed to evaluate GH, IGF-1, and FRUCT concentrations in plasma and FF and their variation across follicle sizes. Sixty ovaries were collected during the breeding season from 30 clinically normal mares raised for meat production. Blood sa...
Mlyneková E, Zaťko S, Halo M, Imrich I, Halo M.This study aimed to examine the seasonal dynamics of non-structural carbohydrates in pasture and their relationship to metabolic indicators in horses with a history of laminitis. Thirty Hucul mares were divided into a laminitis group (LG, = 15) and a control group (CG, = 15). Insulin, glucose, fructosamines concentrations and body weight were monitored during four sampling periods (S0-S3), while pasture variables were analyzed during three periods (S1-S3). The concentration of water-soluble carbohydrates was highest in May (126.8 g/kg DM) and measured lower in October (57.9 g/kg DM), while s...
Yuan X, Yao X, Zeng Y, Wang J, Ren W, Wang T, Li X, Yang L, Yang X, Meng J.The effects of physical exercise on protein expression and metabolites in the plasma exosomes of horses are not yet clear. This study aims to elucidate the effects of exercise training on the expression of plasma extracellular vesicle proteins and metabolites in horses through multi-omics analysis, providing reference indicators for the training and performance evaluation of horses. Methods: Eight healthy 3-year-old horses were selected for the study, with four untrained horses as the control group and four trained horses as the training group. After conducting proteomic and metabolomic an...
So YM, Kwok WH, Tang CWY, Wong COL, Wan TSM, Ho ENM.This paper describes the studies of the in vitro biotransformation of nandrolone decanoate and its metabolic fate in equine plasma and urine after intramuscular administration to castrated thoroughbred horses. The in vitro metabolic study was performed using homogenised horse liver, and the more prominent in vitro biotransformation pathways were found to include hydrolysis, reduction, oxidation and sulfation, mainly resulting in seven Phase I metabolites and one Phase II metabolite. The administration study of nandrolone decanoate was carried out using three retired thoroughbred geldings, e...
Begmatov S, Beletsky AV, Mardanov AV, Lukina AP, Glukhova LB, Karnachuk OV, Ravin NV.Genome reduction and associated metabolic deficiencies have been described in various lineages of parasitic and symbiotic microorganisms that obtain essential nutrients from their partners, and in some free-living microorganisms that inhabit stable environments. The animal gut is a relatively stable ecosystem, characterized by an abundance of organic substances and a high concentration of microorganisms, which provides favorable conditions for the survival of microorganisms with reduced genomes. Metagenomic analysis of 49 samples of feces of farm animals (cows, sheep, yaks, and horses) reveale...
Wermer K, Korbacska-Kutasi O, Berkecz R, Csupor D, Ágh N, Sztojkov-Ivanov A, Cserhalmi D.Cannabidiol (CBD) has shown potential therapeutic benefits in veterinary medicine, but further investigations are needed to establish its pharmacokinetics and therapeutic dosing in horses and ponies. The present study aimed to investigate the pharmacokinetic properties of CBD in Connemara ponies following oral administration of CBD oil. Unassigned: Ten healthy ponies received a single oral dose of CBD oil at 2 mg/kg. Blood samples were collected before dosing and up to 16 days post-administration, with physical examinations conducted at baseline and at 8, 12, and 24 h post-dose. Addition...
Reemtsma FP, Giers J, Horstmann S, Stoeckle SD, Gehlen H.Plasma amino acid (PAA) concentration in horses vary according to the exercise type. This study evaluated the changes in PAA levels and the associated metabolites, urea and ammonia, following short-duration, high-intensity cross-country exercise in eventing horses. Twenty eventing horses participated in 55 rides at 14 international competitions (2* to 4* levels) across five venues in Germany and Poland. Blood samples were collected at four timepoints: before exercise (TP0), at 10 min (TP1), and at 30 min (TP2) post-exercise, as well as in the morning on the day after the competition (TP3). A t...
Sayler B, Manship AJ, Davis J, Taylor J, Gilliam L.Chloramphenicol is a broad-spectrum antibiotic used in equine practice. It is known to produce adverse effects of hyporexia/anorexia after oral administration. Administration per rectum (PR) could mitigate the appetite suppression seen with oral administration and allow its use in horses unable to receive oral medications. The objectives of this study were to evaluate the relative bioavailability of chloramphenicol administered PR or via nasogastric tube (NGT) and determine relevant pharmacokinetic/pharmacodynamic parameters and metabolic ratios. Ten healthy, adult horses were administered chl...
Pipereau K, Trably E, Santa-Catalina G, García-Bernet D, Carrere H.Horse manure is a lignocellulosic biomass found in significant quantities with a vast indigenous flora, not yet fully valorized apart from anaerobic digestion. Its use in the fermentation process can lead to the production of higher-value metabolites. This study investigates three inoculation strategies coupled with five pretreatment conditions for horse manure fermentation. Two microwave pretreatments (200W and 1000W) were compared with a conventional thermal pretreatment, a thermo-acid pretreatment, and an unpretreated condition. The sole horse manure indigenous microorganisms were used in f...
Ho HSM, Mizzi JX, Ho ENM, Wong WT.Ranitidine is a histamine H-receptor antagonist commonly used to treat gastric ulceration in horses. The author's laboratory conducted a study some years ago in the early 2000s on its metabolism as well as its urinary elimination profile in two geldings. With the technology advancement as well as popularity of blood for doping control testing, the laboratory has recently conducted another administration trials of the substance in six horses to study the in vivo metabolism of ranitidine, aiming to identify and reinvestigate the appropriate target(s) for controlling misuse of ranitidine in hors...
Granados MM, Medina-Bautista F, Navarrete-Calvo R, Argüelles D, Domínguez-Pérez JM, Priego-Capote F, Muñoz-Rascón P, Serrano-Rodríguez JM.To date, no intravenous pharmacokinetics (PK) studies have assessed acetaminophen or its major metabolites (acetaminophen-glucuronide and acetaminophen-sulphate) in horses. The influence of sex on acetaminophen metabolism in horses is unclear, and Monte Carlo simulations have not been applied to explore potential clinical applications. This study aimed to determine the intravenous PK and safety of acetaminophen in Andalusian horses at 10 and 20 mg/kg, evaluate sex as a covariate, and simulate clinical regimens. Twenty mares and twenty stallions received intravenous acetaminophen, and plasma ...
Chang X, Zhang Z, Yao X, Meng J, Ren W, Zeng Y.The equine lipid metabolism is activated during and after endurance exercise to provide energy in response to the metabolic and physiological changes in the body caused by prolonged exercise; however, the specific regulatory mechanisms remain controversial and identifying differential lipid metabolites associated with equine endurance is essential to elucidate these regulatory mechanisms. In this study, blood samples for lipid metabolomic analysis and biochemical indices were collected before and after a 26 km race from 12 Yili horses with different endurance performance. The biochemical res...
Kong FKW, Wong ASY, Wan TSM, Ho ENM.Hydrocortisone acetate, a synthetic acetate ester of hydrocortisone, was detected in horse blood samples collected from Thoroughbreds. Hydrocortisone acetate is generally considered an indicator for exogenous administration in horses. As hydrocortisone acetate has been previously reported to be endogenous in selected mammals, a proof-of-concept study was performed to evaluate the possible endogenous nature of hydrocortisone acetate in horses by in vitro incubation experiments using homogenized horse brain tissue.
Van den Branden E, Salamone M, Broothaers K, Peere S, Polfliet E, Dewulf M, Van Steenkiste G, van Loon G, Smits K, Govaere J.The use of transvaginal ultrasound-guided follicle aspiration (TVA) for oocyte collection has become a widely used procedure in horses for embryo production (IVEP). The TVA procedure is characterized by various manipulations, which are physical restraint, perineal preparation, transrectal palpation, insertion of an intravaginal device, and needle punctures. These repeated transvaginal and transovarian punctures have raised concerns about their potential effects on mare welfare. Our study aimed to investigate the effects of TVA manipulations, and especially puncturing, on pain and stress in ma...
Ho HSM, Farrington AF, Ho ENM, Wong WT.2-Hydroxyethyl salicylate (2HES), a nonsteroidal anti-inflammatory drug (NSAID), is a medication to treat musculoskeletal injuries and inflammation swelling of humans and horses. Its misuse could affect the performance of horses and mask injuries, which could pose significant health risks. In horseracing, it is reported as an adverse finding once detected in competition. The metabolism of 2HES in either human or horse has not been reported, and therefore, little is known about its metabolic fate. This paper describes the in vivo metabolism of 2HES in horse with an objective to identify the mo...
Wang T, Meng J, Wang J, Ren W, Yang X, Adina W, Bao Y, Zeng Y, Yao X.The purpose of this study was to explore the relationship between blood lipid levels and the differences in cardiac structure and function of trained and untrained Yili horses as related to exercise performance. We utilized quantitative lipidomics technology to elucidate how the differences in lipid compounds in the blood influenced performance outcomes. Sixteen 18-month-old Yili horses were selected, ten of which received a 15-week training regimen, and six were kept as untrained controls. Cardiac structure and function were assessed by echocardiography, while plasma lipid metabolites were de...
Wang J, Ren W, Li Z, Li L, Wang R, Ma S, Zeng Y, Meng J, Yao X.Equine endurance exercise induces physiological changes that alter metabolism and molecular pathways to maintain balance after intense physical activity. However, the specific regulatory mechanisms remain under debate. Identifying differentially expressed genes (DEGs) and differential metabolites (DMs) associated with equine endurance is essential for elucidating these regulatory mechanisms. This study collected blood samples from six Yili horses before and after an 80 km race and conducted transcriptomics and metabolomics analyses, yielding 722 DEGs and 256 DMs. These DEGs were primarily enri...
Yuan X, Yao X, Zeng Y, Wang J, Ren W, Wang T, Li X, Yang L, Yang X, Meng J.Horse racing may cause stress-induced physiological changes and tissue damage in horses, but the changes in miRNA expression, protein expression, and metabolic substances in the plasma exosomes of the horse after racing are still unclear. This study detected miRNA, protein expression, and metabolic substances in the plasma exosomes of horses before and after competition, providing new insights for post-race recovery and care of horses. Methods: Eight three-year-old horses that had undergone training were selected as the research subjects, with four horses that had not competed as the contr...
Bernabe MCM, Fonseca BB, Silva MVC, Pedrosa IE, Silva MB, Sommerfeld S, de Sousa ALP, de Leva Resende BC, Sousa ACP, Dos Santos Freitas A....Endometritis is one of the main reproductive disorders in mares and due to the increasing prevalence of antibiotic resistance, the use of probiotics in the prevention and treatment of endometritis in mares has gained interest, given their potential to restore and maintain a healthy uterine microbiota. Therefore, the aim of this study was to evaluate the antimicrobial properties of total metabolites of Lactobacillus acidophilus (LA) and Lactiplantibacillus plantarum (LP) against common equine endometrial pathogenic bacteria in vitro (Acinetobacter baumannii, Escherichia coli (1), Escherichia co...
So YM, Kwok WH, Ching CCW, Wong COL, Wan TSM, Ho ENM.Anabolic-androgenic steroids (AAS) are banned substances in both human and equine sports. They are often administered intramuscularly to horses in esterified forms for the purpose of extending their duration of action. As such, the detection of intact esters of endogenous steroids in hair is particularly advantageous, as it can provide unequivocal proof of their external origin. Compared with urine and blood matrices, hair in general allows a longer detection window as long as the administered drug can be incorporated into hair and has not degraded. This can be useful in doping control of equi...
Loos CMM, Zhao S, Li L, Li J, Han W, Vanzant ES, McLeod KR.The objective of this study was to investigate the effect of essential oil (EO) supplementation on insulin sensitivity (IS) and the plasma metabolome in insulin dysregulated (ID) horses. Horses were blocked by degree of IS and assigned randomly to treatment: oral daily bolus (50 mL) of either a plant derived EO supplement or carrier (CON). Mares were housed in dry lots with access to grass hay and supplemented individually twice daily with a concentrate to meet nutrient requirements for mature horses. Before and after 6 wks of treatment, mares underwent a combined glucose-insulin tolerance ...
Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Graiban FM, Ajeebsanu MM, Joseph M, Jose SV.The phosphodiesterase 4 (PDE4) inhibitors constitute a relatively modern class of medications that are known for inducing bronchodilation and exhibiting anti-inflammatory properties within the body. Due to these properties, there is concern regarding their potential misuse as performance-enhancing substances in competitive sports. This study delves into the metabolic conversion of roflumilast in thoroughbred horses following oral administration and in vitro experimentation using equine liver microsomes and Cunninghamella elegans. High-performance liquid chromatography coupled with a Q Exactiv...
Kwak YB, Seo SA, Kim M, Yoon J.Ethyl pyruvate (EP) has emerged as a promising compound with potential therapeutic benefits attributed to its anti-inflammatory and antioxidant properties. This study aimed to understand the effects of EP on plasma metabolites and immune cells in horses, utilizing advanced liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, quantitative polymerase chain reaction (qPCR), and blood chemistry analyses. Our comprehensive analysis detected 2,366 ions, and 126 metabolites were accurately identified. Remarkably, EP administration induced significant changes in 28 metabolites at 1 h a...
Parsad R, Bagiyal M, Ahlawat S, Arora R, Gera R, Chhabra P, Sharma U.Donkeys (Equus asinus) have played a vital role in agriculture, transportation, and companionship, particularly in developing regions where they are indispensable working animals. The domestication of donkeys marked a significant turning point in human history, as they became essential for transportation, agriculture, and trade, especially in arid and semi-arid areas where their resilience and endurance were highly valued. In modern society, donkeys are indispensable due to their diversified applications, including meat, dairy, medicine, and functional bioproducts, supporting economic, cultura...
Božić Jovanović V, Trailović R, Vićić I, Grković N, Radaković M, Karabasil N, Kaić A, Čobanović N.The aim of this study was to determine the effects of loading density and gender on blood welfare indicators, carcass bruises and horsemeat quality. Data were collected from twelve transports of 89 slaughter horses originating from the same collection centre. The transportation of slaughter horses at high loading densities (>200 kg/m), especially stallions, resulted in increased levels of lactate ( = 0.021), glucose ( < 0.0001), ceruloplasmin ( < 0.0001) and AOPP ( < 0.0001), but lower GSH levels ( 200 kg/m) during transport had lower levels of the aforementioned blood metabolites....
Elbourne M, Keledjian J, Cawley A, Fu S.Altrenogest, also known as allyltrenbolone, is a synthetic form of progesterone used therapeutically to suppress unwanted symptoms of estrus in female horses. Altrenogest affects the system by decreasing levels of endogenous gonadotrophin and luteinizing and follicle-stimulating hormones, which in turn decreases estrogen and mimics the increase of progesterone production. This results in more manageable mares for training and competition alongside male horses while improving the workplace safety of riders and handlers. However, when altrenogest is administered, prohibited steroid impurities su...
Galinelli NC, Bamford NJ, Erdody ML, Warnken T, de Laat MA, Sillence MN, Harris PA, Bailey SR.Alpha-methyl-para-tyrosine (AMPT) is a reversible inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This study aimed to determine whether AMPT could reduce dopamine concentrations in horses. Six healthy adult Standardbred geldings were administered AMPT (40 mg/kg BW, orally) or placebo in a randomised crossover study design. Clinical examination findings were recorded, and blood samples were collected for up to 6 h after administration of AMPT or placebo, for measurement of blood glucose, plasma ACTH and cortisol concentrations, and plasma metabolomic anal...
Kwak YB, Stambler I, Yoo HH, Yoon J.Red ginseng (RG), a traditional herbal remedy, has garnered attention owing to its diverse health benefits resulting from its complex composition. However, extensive research is needed to substantiate the efficacy of RG and understand the underlying mechanisms supporting these benefits. This study aimed to identify potential biomarkers and investigate the impact of RG on related metabolic pathways in horse plasma using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. Unassigned: Ten horses were divided into control and RG groups, with the latter administered RG at a dose of ...
Goldansaz SA, Guo AC, Sajed T, Steele MA, Plastow GS, Wishart DS.Metabolomics uses advanced analytical chemistry techniques to comprehensively measure large numbers of small molecule metabolites in cells, tissues and biofluids. The ability to rapidly detect and quantify hundreds or even thousands of metabolites within a single sample is helping scientists paint a far more complete picture of system-wide metabolism and biology. Metabolomics is also allowing researchers to focus on measuring the end-products of complex, hard-to-decipher genetic, epigenetic and environmental interactions. As a result, metabolomics has become an increasingly popular "omics" app...
Li VL, He Y, Contrepois K, Liu H, Kim JT, Wiggenhorn AL, Tanzo JT, Tung AS, Lyu X, Zushin PH, Jansen RS, Michael B, Loh KY, Yang AC, Carl CS....Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1-5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice,...
Daly K, Proudman CJ, Duncan SH, Flint HJ, Dyer J, Shirazi-Beechey SP.We aimed to determine the effects of variations in dietary composition on equine gut microbiota and their fermentation products, and proposed that dietary modifications profoundly affect microbial ecosystems and their metabolites. Bacterial communities within the large intestine of three groups of horses were compared using oligonucleotide-RNA hybridisation methodology. Each group consisting of six horses was maintained on (1) a grass-only diet, (2) a concentrate diet (i.e. supplemented with hydrolysable carbohydrates) and (3) a concentrate diet but horses were affected by simple colonic obstr...
Dougal K, Harris PA, Edwards A, Pachebat JA, Blackmore TM, Worgan HJ, Newbold CJ.The microbiome and associated metabolome of faecal samples were compared to those from the caecum and right dorsal colon of horses and ponies euthanised for nonresearch purposes by investigating the microbial population community structure as well as their functional metabolic products. Through the use of 16S rRNA gene dendrograms, the caecum microbiome was shown to cluster separately from the other gut regions. 16S rRNA gene-based quantitative PCR (q-PCR) also demonstrated differences between the caecum and the other gut regions. Metabolites as identified by Fourier transform infrared cluster...
Möstl E, Messmann S, Bagu E, Robia C, Palme R.After 14C-labelled cortisol infusion in ponies and pigs, faecal samples were collected. Extraction of 0.5 g faeces with 5 ml 80-90% methanol yielded the highest radioactivity in the supernatant. Most of the metabolites were ether soluble. After high performance liquid chromatography (HPLC), the presence of immunoreactive metabolites was demonstrated by measuring each HPLC fraction using enzyme immunoassays for cortisol, corticosterone and 11-oxoaetiocholanolone. Only the assay for 11-oxoaetiocholanolone revealed peaks with co-eluting radioactivity. For biological validation of the test system,...
Schmidt A, Möstl E, Wehnert C, Aurich J, Müller J, Aurich C.Based on plasma cortisol concentrations it is widely accepted that transport is stressful to horses. So far, cortisol release during transport has not been evaluated in depth by non-invasive techniques such as analysis of salivary cortisol and faecal cortisol metabolites. Transport also causes changes in heart rate and heart rate variability (HRV). In this study, salivary cortisol, faecal cortisol metabolites, heart rate and HRV in horses transported by road for short (one and 3.5 h) and medium duration (8 h) were determined. With the onset of transport, salivary cortisol increased immediately...
Lindholm A, Piehl K.LINDHOLM, ARNE and KARIN PIEHL: Acta vet. scand. 1974, , 287–309. — Measurements of metabolites, electrolytes, water, RNA and protein concentrations, the activity of certain muscle enzymes (SDH and PFK) and muscle fibre composition were made on biopsy specimens from the gluteus medius muscle of 68 standardbred horses, ½ to 8 years old. The muscle fibres were classified in 3 major categories, slow twitch (ST), fast twitch and high oxidative (FTH) and fast twitch (FT) fibres. The percentage of FTH fibres was higher after the age of 4 years, averaging 54 %. ST fibres comprised 24 % and this...
Proudman CJ, Hunter JO, Darby AC, Escalona EE, Batty C, Turner C.The intestinal bacterial community of the horse is a key determinant of intestinal and whole body health. Understanding the bacterial community structure and function is an important foundation for studies of intestinal health and disease. Objective: To describe the faecal bacterial community and volatile organic compounds (VOCs) of the faecal metabolome of healthy Thoroughbred racehorses and to characterise responses to dietary supplementation with amylase-rich malt extract. Methods: Intervention study. Methods: Faecal samples were collected noninvasively before and 6 weeks after supplementat...
Fornstedt B, Rosengren E, Carlsson A.The 5-S-cysteinyl derivatives of dopamine, dopa (3,4-dihydroxyphenylalanine) and dopac (3,4-dihydroxyphenylacetic acid) were synthesized and used as reference compounds in high performance liquid chromatography analyses of extracts from various brain regions of eight mammalian species. All three metabolites were detected in the brains of all the species studied. The regional distribution of the metabolites was similar to that of dopamine; the metabolite concentrations ranged from less than 0.1 percent to more than 1 percent of the dopamine level, the highest ratios generally being found in sub...
Czub MP, Venkataramany BS, Majorek KA, Handing KB, Porebski PJ, Beeram SR, Suh K, Woolfork AG, Hage DS, Shabalin IG, Minor W.Serum albumin is the most abundant protein in mammalian blood plasma and is responsible for the transport of metals, drugs, and various metabolites, including hormones. We report the first albumin structure in complex with testosterone, the primary male sex hormone. Testosterone is bound in two sites, neither of which overlaps with the previously suggested Sudlow site I. We determined the binding constant of testosterone to equine and human albumins by two different methods: tryptophan fluorescence quenching and ultrafast affinity extraction. The binding studies and similarities between residu...
Peña FJ, Ortiz-Rodríguez JM, Gaitskell-Phillips GL, Gil MC, Ortega-Ferrusola C, Martín-Cano FE.An overview of the sperm metabolism is presented; using the stallion as a model we review glycolysis, Krebs Cycle and oxidative phosphorylation, paying special attention to the interactions among them. In addition, metabolism implies a series of coordinated oxidation-reduction reactions and in the course of these reactions reactive oxygen species (ROS) and reactive oxoaldehydes are produced ; the electron transport chain (ETC) in the mitochondria is the main source of the anion superoxide and hydrogen peroxide, while glycolysis produces 2-oxoaldehydes such as methylglyoxal as byproducts; due t...
Genzel Y, Behrendt I, König S, Sann H, Reichl U.The production of equine influenza in Madin-Darby canine kidney (MDCK) cells in large-scale microcarrier culture is described with detailed on- and off-line analytical data during cell growth and virus replication. Metabolite concentration profiles for glucose, glutamine, lactate and ammonium are shown. Lactate and ammonium concentrations were always below inhibiting levels. Concentration profiles for essential and non-essential amino acids of the cell culture medium are discussed. During cell growth proline was released into the medium with a significant rate while two amino acids, serine and...
Westermann CM, Dorland L, Votion DM, de Sain-van der Velden MG, Wijnberg ID, Wanders RJ, Spliet WG, Testerink N, Berger R, Ruiter JP, van der Kolk JH.The aim of the current study was to assess lipid metabolism in horses with atypical myopathy. Urine samples from 10 cases were subjected to analysis of organic acids, glycine conjugates, and acylcarnitines revealing increased mean excretion of lactic acid, ethylmalonic acid, 2-methylsuccinic acid, butyrylglycine, (iso)valerylglycine, hexanoylglycine, free carnitine, C2-, C3-, C4-, C5-, C6-, C8-, C8:1-, C10:1-, and C10:2-carnitine as compared with 15 control horses (12 healthy and three with acute myopathy due to other causes). Analysis of plasma revealed similar results for these predominantly...
Lacitignola L, Fanizzi FP, Francioso E, Crovace A.Proton magnetic resonance spectroscopy (1H NMR) has been successfully used in the study of many biological fluids. The data presented here report on the metabolic profiles of normal equine synovial fluids compared with osteoarthritic (OA) fluids. Twenty-five OA synovial fluid samples and eight normal ones were collected from the forelimb fetlock joint in 22 horses, aged between five and 24 years. 1H NMR spectroscopy was carried out with a Bruker Avance DRX 500 equiped with a cryo-magnet working at 11 Tesla, and 'Mestre-C 4.9.9.6' software was used to analyze the spectra. The study assessed the...
Perez de Souza L, Naake T, Tohge T, Fernie AR.The grand challenge currently facing metabolomics is the expansion of the coverage of the metabolome from a minor percentage of the metabolic complement of the cell toward the level of coverage afforded by other post-genomic technologies such as transcriptomics and proteomics. In plants, this problem is exacerbated by the sheer diversity of chemicals that constitute the metabolome, with the number of metabolites in the plant kingdom generally considered to be in excess of 200 000. In this review, we focus on web resources that can be exploited in order to improve analyte and ultimately metabol...
Mach N, Ramayo-Caldas Y, Clark A, Moroldo M, Robert C, Barrey E, López JM, Le Moyec L.Endurance exercise in horses requires adaptive processes involving physiological, biochemical, and cognitive-behavioral responses in an attempt to regain homeostasis. We hypothesized that the identification of the relationships between blood metabolome, transcriptome, and miRNome during endurance exercise in horses could provide significant insights into the molecular response to endurance exercise. For this reason, the serum metabolome and whole-blood transcriptome and miRNome data were obtained from ten horses before and after a 160 km endurance competition. We obtained a global regulatory ...
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...
Ryan D, McKemie DS, Kass PH, Puschner B, Knych HK.The increasing availability of cannabidiol (CBD) and anecdotal reports of its anti-inflammatory effects has garnered it much interest in the equine industry. The objectives of the current study were to (1) describe the pharmacokinetics of oral CBD in exercising thoroughbreds, (2) characterize select behavioral and physiologic effects, and (3) evaluate effects on biomarkers of inflammation using an ex vivo model. This study was conducted in a randomized balanced 3-way crossover design with a two-week washout period between doses. Horses received a single oral dose (0.5, 1, and 2 mg/kg) of CBD...
Liu X, Yao J, Pisha E, Yang Y, Hua Y, van Breemen RB, Bolton JL.Excessive exposure to synthetic and endogenous estrogens has been associated with the development of cancer in several tissues. 4-Hydroxyequilenin (4-OHEN), a major metabolite of equine estrogens present in estrogen replacement formulations, has been shown to induce cytotoxic/carcinogenic effects. In the present study, we have found that 4-OHEN caused DNA damage in breast cancer cells, and cells that contain estrogen receptor alpha (S30) are more sensitive to 4-OHEN-mediated DNA damage as compared to estrogen receptor negative cells (MDA-MB-231). For example, concentration-dependent increases ...
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 ...
Arnold C, Pilla R, Chaffin K, Lidbury J, Steiner J, Suchodolski J.Diarrhea is an adverse effect of antimicrobial therapy in horses. This matched, case-controlled study compared the fecal microbiome and metabolome of horses on antibiotics that developed diarrhea (AAD, = 17) to those that did not develop diarrhea (ABX, = 15) and to a control population not exposed to antibiotics (CON, = 31). Fecal samples were collected from horses that were matched for diet and antimicrobial agent (including dose, route, and duration of therapy). Illumina sequencing of 16S rRNA genes was performed, and QIIME 2.0 was used to generate alpha and beta diversity metrics. Untarg...
Klein DJ, McKeever KH, Mirek ET, Anthony TG.The athletic horse, despite being over 50% muscle mass, remains understudied with regard to the effects of exercise and training on skeletal muscle metabolism. To begin to address this knowledge gap, we employed an untargeted metabolomics approach to characterize the exercise-induced and fitness-related changes in the skeletal muscle of eight unconditioned Standardbred horses (four male, four female) before and after a 12-week training period. Before training, unconditioned horses showed a high degree of individual variation in the skeletal muscle metabolome, resulting in very few differences ...
Anderson JR, Phelan MM, Foddy L, Clegg PD, Peffers MJ.Osteoarthritis is an age-related degenerative musculoskeletal disease characterized by loss of articular cartilage, synovitis, and subchondral bone sclerosis. Osteoarthritis pathogenesis is yet to be fully elucidated with no osteoarthritis-specific biomarkers in clinical use. equine cartilage explants ( = 5) were incubated in tumor necrosis factor-α (TNF-α)/interleukin-1β (IL-1β)-supplemented culture media for 8 days, with the media removed and replaced at 2, 5, and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent one-d...
Arnold CE, Isaiah A, Pilla R, Lidbury J, Coverdale JS, Callaway TR, Lawhon SD, Steiner J, Suchodolski JS.Antibiotic administration can be a cause of gastrointestinal disease in horses, creating a disruption in the normal population and function of bacteria found in the hindgut. The objective of this study was to describe the changes in the cecal and fecal microbiomes and metabolomes of clinically healthy horses before and after metronidazole administration. Metronidazole (15 mg/kg BID PO) was given to five horses with cecal cannulas. The study was suspended on Day 3 due to adverse gastrointestinal effects. Cecal and fecal samples were obtained before (Days minus52, m28, m14, and 0) and after (Day...
Coleman MC, Whitfield-Cargile CM, Madrigal RG, Cohen ND.Metabolic diseases such as obesity and type 2 diabetes in humans have been linked to alterations in the gastrointestinal microbiota and metabolome. Knowledge of these associations has improved our understanding of the pathophysiology of these diseases and guided development of diagnostic biomarkers and therapeutic interventions. The cellular and molecular pathophysiology of equine metabolic syndrome (EMS) and obesity in horses, however, remain ill-defined. Thus, the objectives of this study were to characterize the fecal microbiome, fecal metabolome, and circulating lipidome in obese and non-o...
de Grauw JC, van de Lest CH, van Weeren PR.Articular tissues are capable of producing a range of eicosanoid mediators, each of which has individual biological effects and may be affected by anti-inflammatory treatment. We set out to develop and evaluate a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) approach for the simultaneous analysis of multiple eicosanoid lipid mediators in equine synovial fluid (SF), and to illustrate its use for investigation of the in vivo effects of non-steroidal anti-inflammatory drug (NSAID) treatment. Methods: Synovial fluid samples were obtained from normal joints of 6 adult...
Escalona EE, Leng J, Dona AC, Merrifield CA, Holmes E, Proudman CJ, Swann JR.Metabonomics is emerging as a powerful tool for disease screening and investigating mammalian metabolism. This study aims to create a metabolic framework by producing a preliminary reference guide for the normal equine metabolic milieu. Objective: To metabolically profile plasma, urine and faecal water from healthy racehorses using high resolution (1) H-nuclear magnetic resonance (NMR) spectroscopy and to provide a list of dominant metabolites present in each biofluid for the benefit of future research in this area. Methods: This study was performed using 7 Thoroughbreds in race training at a ...
Snow DH, Harris RC, Gash SP.Four thoroughbred horses performed 4 gallops (G1-G4) with intervals of 5 min. With one exception, gallops were sustained at maximal speed over 620 m. Muscle biopsy samples of the middle gluteal and brachiocephalicus were taken before, during, and after exercise and assayed for ATP and intermediary metabolites. The results showed a major involvement of the brachiocephalicus, in addition to the middle gluteal, during galloping. In three horses, who were clearly fatigued, muscle ATP decreased by up to 50% by the end of G4. This was matched by an equal rise in inosine 5'-monophosphate. Pronounced ...
