Liver function in horses encompasses a range of physiological processes essential for maintaining homeostasis. The liver is responsible for various metabolic, detoxification, and synthetic activities, including the metabolism of carbohydrates, proteins, and fats, as well as the detoxification of endogenous and exogenous substances. It also synthesizes proteins such as albumin and clotting factors, and produces bile necessary for digestion. Liver function can be assessed through biochemical tests that measure enzyme activities and metabolite levels in the blood. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, assessment, and clinical implications of liver function in equine health.
Bergero D, Nery J.The concept 'liver disease' includes several pathological conditions affecting liver's functions. It can either consist of a temporary impaired functioning of the liver and/or it can progress to its failure. The purpose of this review is to update the knowledge on hepatobiliary diseases and in particular on equine hyperlipaemia. Hepatobiliary disease's aetiology, clinical signs, diagnosis and nutritional management are thus described in the first part of the review the second part being devoted to hyperlypaemia's lipid metabolism, epidemiology, clinical signs, post-mortem observations and nutr...
Manso Filho HC, Costa HE, Wang Y, McKeever KH, Watford M.Glutamine plays important roles in the interorgan transport of nitrogen, carbon and energy but little is known about glutamine metabolism in the horse. In this study we determined the tissue distribution of glutamine synthetase expression in three Standardbred mares. Expression of glutamine synthetase was highest in kidney and mammary gland, and relatively high in liver and adipose tissue. Expression was lower in gluteus muscle, thymus, colon and lung, and much lower in small intestine, pancreas and uterus. The pattern of glutamine synthetase expression in the horse is similar to that of other...
Johns IC, Sweeney RW.Liver biopsy is useful in the diagnosis of liver disease in horses. However, bleeding is the major complication. Liver dysfunction can result in abnormalities in coagulation, although there is no definitive association between risk of hemorrhage after biopsy and coagulopathy in humans. Frequency of coagulopathies in horses with liver disease and the nature and frequency of complications after liver biopsy are not reported. Objective: To determine whether there is an association between coagulopathy and hemorrhage after liver biopsy in horses. Methods: Horses with suspected liver disease from w...
Tydén E, Olsén L, Tallkvist J, Tjälve H, Larsson P.Gene and protein expression as well as catalytic activity of cytochrome P450 (CYP) 3A were studied in the nasal olfactory and respiratory mucosa and the tracheal mucosa of the horse. We also examined the activity of NADPH cytochrome P450 reductase (NADPH P450 reductase), the amount of cytochrome b(5) and the total CYP content in these tissues. Comparative values for the above were obtained using liver as a control. The CYP3A related catalytic activity in the tissues of the upper airways was considerably higher than in the liver. The CYP3A gene and protein expression, on the other hand, was hig...
Johns IC, Del Piero F, Wilkins PA.An 11-year-old Thoroughbred broodmare was evaluated for suspected hepatic dysfunction. Clinical signs of hepatic encephalopathy were evident at admission. Hepatic ultrasonographic evaluation revealed an increase in hepatic size, rounded borders and normal echogenicity. There was no evidence of cholelithiasis or bile duct distention. Increased activity of hepatic enzymes, increased bile acid and bilirubin concentration and an increased ammonia concentration were supportive of a diagnosis of hepatic disease and hepatic encephalopathy. Histopathological evaluation of a liver biopsy specimen was c...
Barton MH, LeRoy BE.Reference ranges for serum bile acids (SBA) concentration are well established in healthy adult horses. Increased values are indicative of hepatic disease. Objective: SBA concentrations are significantly greater in the neonatal period compared with mature horses, and illness in the neonatal period will further increase SBA. Methods: Ten healthy mature horses, 12 healthy foals, and 31 clinically ill foals. Methods: Prospective cross-sectional study. Blood samples were obtained once from the mature horses, from healthy foals immediately after birth, at 2 days, and at 1, 2, 3, 4, and 6 weeks of a...
Ho EN, Leung DK, Leung GN, Wan TS, Wong HN, Xu X, Yeung JH.Mesterolone (1alpha-methyl-5alpha-androstan-17beta-ol-3-one) is a synthetic anabolic androgenic steroid (AAS) with reported abuses in human sports. As for other AAS, mesterolone is also a potential doping agent in equine sports. Metabolic studies on mesterolone have been reported for humans, whereas little is known about its metabolic fate in horses. This paper describes the studies of both the in vitro and in vivo metabolism of mesterolone in racehorses with an objective to identify the most appropriate target metabolites for detecting mesterolone administration. In vitro biotransformation st...
Loynachan AT, Williams NM, Freestone JF.A 5-day-old Thoroughbred foal was submitted to the necropsy service at the University of Kentucky Livestock Disease Diagnostic Center. The foal had a clinical history of seizure activity and severe icterus. A complete blood count and serum chemistry analysis indicated that the foal was anemic (hematocrit, 16%), hyperbilirubinemic (45 mg/dl), and hypoglycemic. At necropsy, all tissues were discolored various shades of yellow. Microscopically, there was degeneration and necrosis of cerebral neurons and cerebellar Purkinje cells; severe hepatocellular degeneration and necrosis; and deposition of ...
Loynachan AT, Bolin DC, Hong CB, Poonacha KB.Hepatoblastoma was diagnosed in 3 Thoroughbreds at the University of Kentucky Livestock Disease Diagnostic Center (LDDC) since 1997. Case #1 involved a fetus with a well-demarcated, multilobulated, solitary mass that extended from the left liver lobe. Case #2 was observed in a neonate with a primary hepatic mass and multiple metastases in the skin, brain, meninges, and stylohyoid bone. Case #3 was a solitary hepatic mass incidentally discovered in a neonate at necropsy. Microscopically, the masses were similarly composed of sheets and cords of fetal and embryonal epithelial cells that frequent...
Brown DL, Anderson M, Cullen JM.Mesenchymal hamartoma of the liver is a rare congenital disorder of biliary tract development. During the necropsy of a late-term equine fetus, a markedly enlarged liver of more than two times normal weight was found. Light microscopic review revealed that the normal hepatic parenchyma had been obliterated, replaced, and expanded by abnormal bile ducts surrounded by abundant, myxoid stroma. The lesion was diagnosed as a mesenchymal hamartoma. Small portions of the liver had bridging septa of fibrosis and proliferations of small-caliber abnormal bile ducts, resembling another congenital biliary...
Johnson AL, Divers TJ, Freckleton ML, McKenzie HC, Mitchell E, Cullen JM, McDonough SP.Fourteen horses at a boarding stable in Virginia were diagnosed with hepatic disease and locally grown hay was implicated as the cause. Objective: Panicum dichotomiflorum, the predominant grass species in the hay, is hepatotoxic to horses. Methods: Naturally occurring cases were adult horses of various breeds. Two healthy adult horses and 2 healthy adult sheep were used in feeding trials. Methods: Blood and liver specimens collected from affected animals during the outbreak were analyzed. Some of the affected animals were treated supportively; the main intervention was hay withdrawal. Feeding ...
Borchers A, Magdesian KG, Halland S, Pusterla N, Wilson WD.Tyzzer's disease is a rapidly progressive and highly fatal hepatitis of foals caused by Clostridium piliforme. Survival of a confirmed case has not been reported previously. Objective: Successful therapy of C. piliforme infection in foals is possible. Polymerase chain reaction (PCR) can be used to diagnose Tyzzer's disease antemortem or postmortem. Methods: Seven foals were included in the study. Methods: Retrospective study was made to evaluate the clinical and pathologic characteristics of foals with Tyzzer's disease. Medical records of the Veterinary Medical Teaching Hospital at University ...
Ho EN, Kwok WH, Leung DK, Wan TS, Wong AS.Turinabol (4-chloro-17alpha-methyl-17beta-hydroxy-1,4-androstadien-3-one) is a synthetic oral anabolic androgenic steroid. As in the case of other anabolic steroids, it is a prohibited substance in equine sports. The metabolism of turinabol in human has been reported previously; however, little is known about its metabolic fate in horses. This paper describes the studies of both the in vitro and in vivo metabolism of turinabol in racehorses with an objective to identify the most appropriate target metabolites for detecting turinabol administration. For the in vitro studies, turinabol was incub...
Szeredi L, Haake DA.The aim of this study was to examine the utility of immunohistochemistry (IHC) in the diagnosis of leptospiral equine abortion and to compare IHC to silver staining and serology of the aborted mares. Ninety-six fetuses from 57 farms were examined using all 3 diagnostic techniques, revealing evidence of leptospiral infection in 3 fetuses (3.1%) from 3 (5.3%) different farms. A new finding in 1 of these confirmed cases of leptospiral abortion was the presence of macroscopic pinpoint grayish-white nodules that had a histologic correlate of hepatic necrosis; other histologic findings were consiste...
Peyrou M, Bousquet-Melou A, Laroute V, Vrins A, Doucet MY.Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat severe bacterial infections in horses. A repeated measures study has been designed to compare their pharmacokinetic parameters, to investigate their bioavailability and to estimate their absorbed fraction and first-pass effect by using plasma, urinary and metabolite data collected from five healthy mares. Clearance and V(d(ss)) were greater for enrofloxacin (mean +/- SD = 6.34 +/- 1.5 mL/min/kg and 2.32 +/- 0.32 L/kg, respectively) than for marbofloxacin (4.62 +/- 0.67 mL/min/kg and 1.6 +/- 0.25 L/kg, respectively...
Patton KM, Peek SF, Valentine BA.A 17-year-old Quarter horse mare was referred to Cornell University for postmortem examination after 72 hours of encephalopathy that consisted of depression, mania, and blindness. A plasma sample and cerebral spinal fluid demonstrated hyperammonemia. Gross necropsy examination findings included the following: mild icterus, a transmural mass in the glandular portion of the gastric fundus, multiple masses throughout the liver, and a large tumor thrombus in the portal vein. Microscopically, the gastric mass, hepatic masses, and portal vein thrombus were composed of similar neoplastic epithelial c...
Knobloch M, Portier CJ, Levionnois OL, Theurillat R, Thormann W, Spadavecchia C, Mevissen M.Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 microg/ml S-ketamine over 120 ...
Oikawa S, McGuirk S, Nishibe K, Higuchi T, Kurosawa T, Watanuki M, Satoh H.Hyperlipemia in horses is a disorder of lipid metabolism peculiar to ponies. This study reports changes of blood biochemical values from the acute to the postconvalescent phases in 3 Shetland ponies with hyperlipemia in Japan. Diseased ponies (all 7 to 9 years old, in late pregnancy, and obese) were fed in the same farm. The periods of their hospitalizations ranged from 30 to 45 days. Twelve well-conditioned ponies (3 to 13 years old) around parturition were used to establish baseline values for blood test results. Main clinical findings in the affected ponies were depression, dysphagia, anore...
Szeredi L, Molnár T, Glávits R, Takai S, Makrai L, Dénes B, Del Piero F.Rhodococcus equi was isolated from lung, liver, spleen, and stomach content of two aborted equine fetuses of 7 and 8 months gestation from two different farms. Lesions included diffuse pyogranulomatous pneumonia with numerous Gram-positive coccobacilli within the cytoplasm of macrophages, multinucleated Langhans giant cells and neutrophils, and enhanced extramedullary hematopoiesis with megakaryocytosis within the liver and spleen. Detection of R. equi was made by bacteriology and immunohistochemistry for R. equi and VapA, the virulence factor of R. equi. R. equi and VapA were identified withi...
Gusson F, Carletti M, Albo AG, Dacasto M, Nebbia C.To complete a studyaimed at investigating the pattern of the basal activities of liver xenobioticmetabolizing enzymes in major and minor species intended for meat production, microsomal carboxylesterases and some conjugating enzyme activities were determined and compared in liver preparations from horses, cattle, pigs, rabbits and broiler chicks, using the rat as a reference species. Horses and broiler chicks exhibited a lower microsomal carboxylesterase activity towards indophenyl or p-nitrophenyl acetate than that measured in cattle or pig subfractions. Among food-producing species, the rate...
Gee EK, Firth EC, Morel PC, Fennessy PF, Grace ND, Mogg TD.To determine the influence of copper (Cu) supplementation by injection of mares in late gestation on the frequency and severity of osteochondrosis (OC) lesions in their foals at around 160 days of age. To determine if there was any influence of the concentration of Cu in the liver, growth rate, birthweight, weight at 160 days of age, fatness, sex, or year of birth of the foal on the frequency and severity of OC lesions. To determine the influence of dam's age, and sex and birthweight of the foal on the growth rate from birth to 160 days of age, and weight at 160 days of age. Methods: Thirty-th...
Gee EK, Firth EC, Morel PC, Fennessy PF, Grace ND, Mogg TD.To assess the relationship between the radiographic and microscopic appearance of the physeal regions of the distal third metacarpal (Mc3) and metatarsal (Mt3) bones of Thoroughbred foals at 160 days of age, and to clinically assess changes in contour of the distal Mc3 and Mt3 physeal regions from birth to 160 days of age. To assess relationships between maximum clinical physis scores and age, time of year, foal's sex, condition score, growth rate, copper (Cu) concentration in the liver of the foal, and supplementation of the dam with Cu in late gestation. Methods: Dams were given Cu (n=5 and ...
Gee E, Davies M, Firth E, Jeffcott L, Fennessy P, Mogg T.Copper (Cu) supplementation of dams in late gestation may be protective against articular cartilage abnormalities in foals. Articular cartilage was harvested from 22 Thoroughbred foals at 160 days of age, at sites predisposed to osteochondrosis (OC), and examined for evidence of early cartilage abnormalities and established dyschondroplastic (DCP) lesions to determine if there were any significant differences due to mare Cu supplementation by injection during late gestation, or foal liver Cu concentration. Cu supplemented mares received calcium Cu edetate injections in late gestation (250 mg a...
Boyle AG, Magdesian KG, Ruby RE.To assess data regarding clinical features, clinicopathologic and blood gas variables, and outcome from horse and mule foals with confirmed neonatal isoerythrolysis (NI). Methods: Retrospective case series. Methods: 17 horse and 1 mule foals. Methods: Medical records of foals (< 14 days old) with NI were reviewed. Information collected included signalment; clinical examination findings; results of hematologic, serum and plasma biochemical, and venous blood gas analyses and urinalysis; treatments; and outcome. Results: Data from 17 horse foals and 1 mule foal with NI (mean age, 71 hours) were e...
Semioshkina N, Voigt G, Fesenko S, Savinkov A, Mukusheva M.The radiological assessment of the impact of nuclear weapon's testing on the Semipalatinsk Test Site (STS) on the local population requires comprehensive site-specific information on radionuclide behaviour in the environment. However, information on radionuclide behaviour in the conditions of the STS is rather sparse and, in particular, there are no data in the literature on parameters of radionuclide transfer from feed to horse products proofed to be important contributors to the internal dose to the local population. The transfer of 137Cs and 90Sr to horse milk and meat was studied under lab...
Gardner RB, Nydam DV, Mohammed HO, Ducharme NG, Divers TJ.The purpose of this study was to test the hypothesis that horses with right dorsal displacement of the large colon (RDDLC) have elevations in serum gamma glutamyl transferase (GGT) activity when compared with horses with left dorsal displacement of the large colon (LDDLC). Medical records from 37 horses with RDDLC and 48 horses with LDDLC were reviewed. Horses were included for study if the RDDLC or LDDLC was confirmed by exploratory laparotomy or postmortem examination and if a serum GGT measurement was obtained within 24 hours before surgery. The proportion of horses with GGT activity within...
Sellon DC, Spaulding K, Breuhaus BA, Katz L, Mealey R.Hepatic abscesses were diagnosed in 3 adult horses. Two were < 4 years old and had evidence of concurrent immune-mediated conditions, including aseptic arthritis, immune-mediated thrombocytopenia, and immune-mediated anemia. Predisposing factors for hepatic abscess formation in these horses included prior abdominal surgery, proximal duodenitis/jejunitis, inflammatory bowel disease, and a penetrating foreign body in the large colon. Serum hepatic enzyme activities were within or slightly greater then reference limits in all 3 horses. The most pronounced and consistent abnormalities on CBC and s...
Marycz K, Bourebaba N, Serwotka-Suszczak A, Mularczyk M, Galuppo L, Bourebaba L.Equine metabolic syndrome (EMS) is recognized as one of the leading cause of health threatening in veterinary medicine worldwide. Recently, PTP1B inhibition has been proposed as an interesting strategy for liver insulin resistance reversion in both equines and humans, however as being a multifactorial disease, proper management of EMS horses further necessities additional interventional approaches aiming at repairing and restoring liver functions. In this study, we hypothesized that in vitro induction of Eq_ASCs hepatogenic differentiation will generate a specialized liver progenitor-like cell...
Barrell EA.Polyuria and polydipsia are rare, but significant, manifestations of several different diseases of horses. Causes can be endocrine, iatrogenic, psychogenic, infectious, or toxic in nature and can also be due to primary renal disease or diseases of other organs, such as the liver. Although numerous causes of polyuria and polydipsia in horses exist, the most common conditions include chronic kidney disease, pituitary pars intermedia dysfunction, and psychogenic polydipsia with secondary polyuria. Additional testing is dictated by history, other clinical signs, and the results of blood work and/o...
Montesissa C, Stracciari JM, Fadini L, Beretta C.A comparison has been made of the in vitro metabolism of febantel (FBT) with that of one of its pharmacologically active metabolites fenbendazole (FBZ) using microsomal preparations from liver of sheep, calf, horse, pig, rat, chicken and trout. The oxidation of FBT to the corresponding sulphoxide appeared to be far more rapid with the exception of the trout, than a similar reaction with FBZ. Indeed FBT was further metabolized in several species by cyclization and further oxidation. This observation could have toxicological significance in view of the greater tetratogenic effects of the metabol...
Leo M, Kolb E, Siebert P, Dittrich H.The activity of adenosine deaminase in the cerebrum, cerebellum, brain stem, heart, skeletal muscle, lung, liver, spleen, kidney and testes of horses of the breeds Haflinger and Thüringer Kaltblut was not different from each other. In the erythrocytes and the plasma no activity of the ADA exists.
Kumanomido T, Kamada M, Wada R, Kenemaru T, Sugiura T, Akiyama Y.Sagiyama virus is a member of the Getah virus group. Its pathogenicity for horses was examined. All the horses infected with the original 4 strains of Sagiyama virus (M6/Mag 33, Mag 121, Mag 132 and Mag 258) developed pyrexia ranging from 39.0 to 40.0 degrees C. Other clinical signs, characterized by eruptions, edema in the hind legs, enlargement of the submandibular lymph node and mild leukopenia, were also manifested. Viremia occurred 1-4 days post-inoculation (p.i.). Virus was recovered from spleen, liver, lung and various lymph nodes of a horse autopsied on Day 4 p.i. The maximum titer of ...
Mendonça MFF, Pimentel LA, Leal PV, Oliveira Filho JC, Caymmi LG, Silva AWO, Jesus RS, Peixoto TC.This study aimed to describe the first reports of outbreaks of hepatogenous photosensitization in cattle, sheep, and horses caused by spontaneous ingestion of Chamaecrista serpens, as well as to reproduce poisoning in sheep experimentally. Eleven photodermatitis outbreaks of unknown cause occurred in cattle, sheep and horses on nine farms in the semiarid region of Bahia, northeastern Brazil, between July 2017 and July 2020. Cutaneous lesions of photosensitization initiated until one week after the animals were introduced in paddocks invaded by the plant at the beginning of the rainy season. Th...
Nishita T, Matsushita H.A sensitive sandwich enzyme immunoassay (EIA) for measuring equine carbonic anhydrase III (CA-III) was established using a microplate as a solid-phase and peroxidase as a labelling enzyme. The assay can detect concentrations as low as 5 ng/ml using 20 microliters of sample sera. Within-run coefficients of variation obtained using standard equine CA-III were less than 5 per cent. CA-III levels in equine serum ranged from 5 to 50 ng/ml (n = 370), and apparently abnormal levels of CA-III from 100 to 1900 ng/ml (n = 27) were observed. The concentrations of immunoreactive CA-III in the extracts of ...
Aminlari M, Vaseghi T.1. A new colorimetric method was used for determination of arginase in different tissues of some domestic animals. 2. In all species studied liver was the richest source of arginase. 3. Significant differences were observed in the specific activity of arginase in livers from different species. 4. In all species, besides liver, kidney and brain also contained significant levels of arginase. 5. In the dog, in addition to the three organs mentioned above, lung, heart, spleen and skeletal muscle showed some arginase activity. 6. In sheep and cattle significant arginase activity was observed in the...
Loynachan AT, Bolin DC, Hong CB, Poonacha KB.Hepatoblastoma was diagnosed in 3 Thoroughbreds at the University of Kentucky Livestock Disease Diagnostic Center (LDDC) since 1997. Case #1 involved a fetus with a well-demarcated, multilobulated, solitary mass that extended from the left liver lobe. Case #2 was observed in a neonate with a primary hepatic mass and multiple metastases in the skin, brain, meninges, and stylohyoid bone. Case #3 was a solitary hepatic mass incidentally discovered in a neonate at necropsy. Microscopically, the masses were similarly composed of sheets and cords of fetal and embryonal epithelial cells that frequent...
Srihakim S, Swerczek TW.Parasite-free pony foals (n = 10) were infected orally with 1000,000 Parascaris equorum embryonated eggs. One pony foal each was euthanatized on days 1, 3, 5, 7, 11, 16, 23, 27, 42, or 80 after infection. Foals infected for more than 7 days showed signs of coughing, anorexia, rough coat, and weight loss. Cellular changes in the blood were mild anemia, marked eosinophilia, and leukopenia. Gross postmortem lesions included hemorrhage, edema, and white-to-yellow necrotic foci (0.5 to 1.00 mm) in lungs, liver, and bronchial and hepatic lymph nodes. Microscopically, the liver was hemorrhagic and ha...
Inkerman PA, Scott K, Runnegar MT, Hamilton SE, Bennett EA, Zerner B.Chicken, sheep, and horse liver carboxylesterases have been purified by procedures involving ammonium sulfate fractionation, ion-exchange chromatography and gel filtration on Sephadex. The actual yields of the procedures described were as follows: chicken, 1 g from 2 kg of liver powder (chloroform-acetone); sheep, 200 mg from 400 g of powder (chloroform-acetone); horse, 230 mg from 800 g of powder (acetone). The purified enzymes are free of non-carboxyl-esterase protein as shown by gel electrophoresis, although they do contain electrophoretic variants. The equivalent weight of the chicken enzy...
Tydén E, Bjornstrom H, Tjälve H, Larsson P.The gene and protein expression and the cellular localization of the ABC transport proteins breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance-associated protein 2 (MRP2) have been examined in the intestines, liver and kidney in horse. High gene and protein expression of BCRP and MRP2 were found in the small intestines, with cellular localization in the apical membranes of the enterocytes. In the liver, MRP2 was present in the bile canalicular membranes of the hepatocytes, whereas BCRP was localized in the cytoplasm of hepatocytes...
Schmitz A, Zielinski J, Dick B, Mevissen M.Testosterone (TES) 6-β-hydroxylation is a significant metabolic step in the biotransformation of TES in human liver microsomes and reflects cytochrome P450 (CYP) 3A4/5 specific metabolic activity. Several CYP3A enzymes have been annotated in the horse genome, but functional characterization is missing. This descriptive study investigates TES metabolism in the horse liver in vitro and the qualitative contribution of three CYP3A isoforms of the horse. Metabolism of TES was investigated by using equine hepatocyte primary cultures and liver microsomes. Chemical inhibitors were used to determine t...
Koizumi N, Inoue Y, Ninomiya R, Fujita D, Tsukamoto T.The concentrations of Cd, Zn, Cu, and metallothionein (MT) in the liver, renal cortex, and renal medulla were determined in 24 male and 15 female younger thoroughbreds (age 27 to 97 months) and two old male horses (age 154 months and 190 months). High correlations were found between Zn and MT in the liver (partial correlation coefficient 0.836), between Cd and MT in the renal cortex (partial correlation coefficient 0.786), and between Cd and Zn in the renal cortex (partial correlation coefficient 0.675), while the correlation between Cd and MT in the liver was low (partial correlation coeffici...
Fenwick SJ, Scarth JP.Within horseracing, the detection of prohibited substance doping often requires urine analysis; hence, it is necessary to understand the metabolism of the drugs in question. Here, the previously unknown equine metabolism of eight sedatives is reported in order to provide information on target metabolites for use in doping control. Phase I metabolite information was provided by incubation with equine liver S9 fraction. In vitro techniques were chosen in order to reduce the ethical and financial issues surrounding the study of so many compounds, none of which are licensed for use in horses in th...
Mutlib AE, Chui YC, Young LM, Abbott FS.The metabolic fate of xylazine, 2-(2,6-dimethylphenylamino)-5,6-dihydro-4H-1,3-thiazine, in horses is described. The major metabolites identified in the hydrolyzed horse urine were 2-(4'-hydroxy-2',6'-dimethylphenylamino)-5,6-dihydro-4H-1,3-thiazi ne, 2-(3'-hydroxy-2',6'-dimethylphenylamino)-5,6-dihydro-4H-1,3-thiazi ne, N-(2,6-dimethylphenyl)thiourea, and 2-(2',6'-dimethylphenylamino)-4-oxo-5,6-dihydro-1,3-thiazine. These metabolites were also produced by incubating xylazine with rat liver microsomes. The major metabolite produced in vitro by rat liver preparations was found to be the ring op...
Satué K, Fazio E, Medica P, Miguel L, Gardón JC.In the present review, the authors, based on the multiple functions performed by the liver, analyze the multiple biochemical and hematological changes as an expression of altered liver function in the horse. The liver performs important metabolic functions related to the synthesis, degradation, and excretion of various substances. Modification of these functions can be evaluated and diagnosed by determining serum concentrations of several serum analytes, including enzymes and other endogenous substances. Hepatocellular enzymes, such as sorbitol dehydrogenase-SDH and glutamate dehydrogenase-GLD...
Nilsson K, Larsson PO.Horse liver alcohol dehydrogenase was immobilized on glycerylpropyl-silica (10 micron, 1000-A pores) activated with 2,2,2-trifluoroethanesulfonyl chloride (tresyl chloride). The coupling and activity yield was almost 100%. The coenzyme-binding sites were equivalent and virtually unaffected by the immobilization process, as judged from Scatchard plots and active-site titrations. The silica-bound enzyme, packed in steel columns, was integrated with HPLC equipment and then successfully used for chromatography of adenine nucleosides, adenine nucleotides, and triazine dyes. Dissociation constants w...
Johns IC, Del Piero F, Wilkins PA.An 11-year-old Thoroughbred broodmare was evaluated for suspected hepatic dysfunction. Clinical signs of hepatic encephalopathy were evident at admission. Hepatic ultrasonographic evaluation revealed an increase in hepatic size, rounded borders and normal echogenicity. There was no evidence of cholelithiasis or bile duct distention. Increased activity of hepatic enzymes, increased bile acid and bilirubin concentration and an increased ammonia concentration were supportive of a diagnosis of hepatic disease and hepatic encephalopathy. Histopathological evaluation of a liver biopsy specimen was c...
Takeda S, Ohta M, Ebina S, Nagayama K.Horse L-ferritin cDNA was cloned from horse liver, and the base sequence was determined. The L-ferritin was expressed using pTZ18U encoding lac promoter, and found to possess an additional 8-amino acid sequence at the N-terminus as compared with commercially obtained horse spleen (natural) ferritin. It was determined that there was Pro at position 94 in both the recombinant and natural L-ferritin, although it was previously reported that Leu was in this position in the natural species. Transmission electron microscopy showed that this recombinant ferritin formed a 24-mer shell.
Delvescovo B, Tomlinson J, DeNotta S, Hodge E, Bookbinder L, Mohammed HO, Divers TJ.Serum biochemistry results and presence of fibrosis on liver biopsies are frequently used as prognostic indicators in horses with liver dysfunction. The objective of this retrospective multicenter study was to determine if the magnitude of abnormal liver specific biochemical tests such as bile acids (BA), direct bilirubin and gamma-glutamyltransferase (GGT), or the presence of fibrosis reported on liver biopsies was associated with prognosis in horses with liver dysfunction. Eighty-two horses older than one year, examined at four referral hospitals in the eastern United States, with BA values ...
Argiroudis SA, Kent JE, Blackmore DJ.The isoenzymes of creatine kinase have been measured in serum and selected tissues from horses. The distribution followed that reported in other species in that the MM dimer of the isoenzyme was present in voluntary and non-voluntary muscle, thyroid, liver, spleen, lung and intestine. The BB dimer of the isoenzyme was predominant in brain, pancreas, kidney, intestine, lung, spleen, liver and thyroid. In contrast, in 4 hearts examined less than 1.5 per cent of the total creatine kinase activity was attributable to the MB form of the isoenzyme. The MB isoenzyme was, however, present in intestine...
Szeredi L, Molnár T, Glávits R, Takai S, Makrai L, Dénes B, Del Piero F.Rhodococcus equi was isolated from lung, liver, spleen, and stomach content of two aborted equine fetuses of 7 and 8 months gestation from two different farms. Lesions included diffuse pyogranulomatous pneumonia with numerous Gram-positive coccobacilli within the cytoplasm of macrophages, multinucleated Langhans giant cells and neutrophils, and enhanced extramedullary hematopoiesis with megakaryocytosis within the liver and spleen. Detection of R. equi was made by bacteriology and immunohistochemistry for R. equi and VapA, the virulence factor of R. equi. R. equi and VapA were identified withi...
Starzonek J, Roscher K, Blüher M, Blaue D, Schedlbauer C, Hirz M, Raila J, Vervuert I.In horses and ponies numerous medical conditions are known to be linked with inflammation in different tissues, especially in the liver. Besides affecting other metabolic pathways such as the expression of certain interleukins (IL), inflammation is associated with stress of the endoplasmic reticulum (ER). In particular, ER stress leads to adaptive stress response and can be measured by several markers of inflammatory and stress signalling pathways, like nuclear factor κB (NF-kB). Objective: To investigate lipopolysaccharide (LPS)-induced inflammatory reactions and their modulation in horses 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 ...
Noonan NE.Adult female dogs or pony mares were subjected to a nonlethal dose of CCl4 (0.5 ml/kg of body weight). Amounts of several plasma enzymes thought to be indicative of hepatic disease were monitored. Plasma enzymes alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), arginase, gamma-glutamyltransferase (GGT), and iditol dehydrogenase (ID), as well as total plasma bilirubin, were determined in these animals before and after the administration of the CCl4. In the dog, GGT was not significantly increased, whereas ALP values were increased during days 1 to 6. In the...
Oliveira-Filho JP, Cagnini DQ, Badial PR, Pessoa MA, Del Piero F, Borges AS.Cassia occidentalis is a bush from the Leguminosae family, subfamily Caesalpinoideae, and is a toxic plant of veterinary interest due to the occasional contamination of animal rations. This report describes the clinical and histopathological findings of an outbreak of C. occidentalis poisoning in horses. Twenty mares were poisoned after consuming ground corn contaminated with 8% of C. occidentalis seeds. Of the 20 animals affected, 12 died: 8 mares were found dead, 2 died 6 h after the onset of clinical signs compatible with hepatic encephalopathy and the 2 other animals were subjected to euth...
Haechler S, Van den Ingh TS, Rogivue C, Ehrensperger F, Welle M.Congenital hepatic fibrosis with autosomal recessive or dominant inheritance has been described in humans, cats, piglets, and dogs. In horses, only two cases of congenital hepatic fibrosis have been previously reported. This retrospective study of records from the Institute for Animal Pathology, University of Berne, identified 30 foals with liver lesions compatible with congenital hepatic fibrosis. Anamnestic data revealed clinical signs of severe liver injury in most affected animals. Pathologic examination showed severely enlarged, firm livers with thin-walled cysts. Histologically, the live...
Sanny CG, Weiner H.The inhibition of mitochondrial (pI 5) horse liver aldehyde dehydrogenase by disulfiram (tetraethylthiuram disulphide) was investigated to determine if the drug was an active-site-directed inhibitor. Stoichiometry of inhibition was determined by using an analogue, [35S]tetramethylthiuram disulphide. A 50% loss of the dehydrogenase activity was observed when only one site per tetrameric enzyme was modified, and complete inactivation was not obtained even after seven sites per tetramer were modified. Modification of only two sites accounted for a loss of 75% of the initial catalytic activity. Th...
