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.
Caloni F, Cortinovis C.Fumonisins, trichothecenes and zearalenone are the most commonly occurring Fusarium mycotoxins in cereal grains and animal feed. In this review, the toxicity of these mycotoxins in horses is considered with particular reference to recent data on specific and proposed syndromes. Compared to other animal species, very little information is available on the adverse effects of fusariotoxins in horses. Fumonisin B(1) (FB(1)) is the causative agent of leukoencephalomalacia, which is typified by depression, aimless circling, head pressing, paresis, ataxia, blindness and death. FB(1) has also been sho...
Schmitz A, Theurillat R, Lassahn PG, Mevissen M, Thormann W.CE with multiple isomer sulfated-CD as selector was used for the simultaneous analysis of the stereoisomers of ketamine, norketamine, 5,6-dehydronorketamine and hydroxylated metabolites of norketamine in liquid/liquid extracts of (i) in vitro incubations with ketamine or norketamine and equine liver microsomes and (ii) plasma and urine of ponies receiving a target-controlled infusion of ketamine under isoflurane anesthesia. Hydroxynorketamine metabolites with the hydroxy group at the cyclohexanone ring could be shown to be formed stereoselectively both in vitro and in vivo. Due to the lack of ...
Capponi L, Schmitz A, Thormann W, Theurillat R, Mevissen M.To investigate cytochrome P450 (CYP) enzymes involved in metabolism of racemic and S-ketamine in various species and to evaluate metabolic interactions of other analgesics with ketamine. Methods: Human, equine, and canine liver microsomes. Methods: An analgesic was concurrently incubated with luminogenic substrates specific for CYP 3A4 or CYP 2C9 and liver microsomes. The luminescence signal was detected and compared with the signal for negative control samples. Ketamine and norketamine enantiomers were determined by use of capillary electrophoresis. Results: A concentration-dependent decrease...
Bentz KJ, Burgess BA, Lohmann KL, Shahriar F.A 4-year-old Belgian mare was presented with a 1-week history of fever, suspected of being caused by peritonitis. The mare died before the diagnostic procedures had been completed; postmortem examination revealed torsion of the left medial lobe of the liver, resulting in diffuse necrosis of liver tissue and severe peritoneal effusion. Une jument belge de 4 ans est présentée avec une anamnèse de fièvre qui persiste depuis 1 semaine, que l’on soupçonne causée par une péritonite. La jument est morte avant l’achèvement des procédures diagnostiques; l’autopsie a révélé une torsio...
Tydén E, Tallkvist J, Tjälve H, Larsson P.P-glycoprotein (P-gp) is an important drug transporter, which is expressed in a variety of cells, such as the intestinal enterocytes, the hepatocytes, the renal tubular cells and the intestinal and peripheral blood lymphocytes. We have studied the localization and the gene and protein expression of P-gp in these cells in horse. In addition we have compared the protein sequence of P-gp in horse with the protein sequences of P-gp in several other species. Real time RT-PCR and Western blot showed gene and protein expression of horse P-gp in all parts of the intestines, but there was no strict cor...
Hughes KJ, McGorum BC, Love S, Dixon PM.Six ponies and four horses with a mean (sd) age of 15.9 (6.0) years developed sudden-onset bilateral laryngeal paralysis (BLP) in association with hepatic dysfunction. Nine of them had been referred for the investigation of respiratory distress, and one pony had been referred for weight loss before BLP developed. Nine of the animals had clinicopathological evidence of liver disease, and nine had histological evidence of liver disease. All of the animals had one or more of the following: hepatic encephalopathy (in eight), hyperammonaemia (in six) and endoscopic evidence of BLP (in nine). Three ...
Saulez MN, Burton A, Steyl JC, Williams JH, Clift SJ.The medical records of four horses whose intestines had been perforated by metallic wires were reviewed. Three of the horses developed acute colic, and the other progressively lost weight and became inappetent and pyrexic. Metallic wires were detected either by exploratory laparotomy or postmortem examination. In three of the horses there were adhesions containing an encapsulated metallic wire in the small intestine, and in the other the wire was contained within an abscess with multiple adhesions involving the liver, spleen and mesentery.
Germann SE, Richter M, Schwarzwald CC, Wimmershoff J, Spiess BM.A 6-year-old thoroughbred gelding was presented with a history of blepharospasm and opacity in the OS of 1 weeks' duration. Ophthalmic examination findings were consistent with acute uveitis in the OS, and traditional treatment was initiated with systemic antibiotics and anti-inflammatory drugs, topical mydriatics, and corticosteroids. During the total treatment period of 4 weeks response to treatment was weak and the horse developed further problems such as cellulitis of the right hind limb with fever and eventually weight loss and dependent edema. Blood work was indicative of liver disease. ...
Schmitz A, Portier CJ, Thormann W, Theurillat R, Mevissen M.Stereoselectivity has to be considered for pharmacodynamic and pharmacokinetic features of ketamine. Stereoselective biotransformation of ketamine was investigated in equine microsomes in vitro. Concentration curves were constructed over time, and enzyme activity was determined for different substrate concentrations using equine liver and lung microsomes. The concentrations of R/S-ketamine and R/S-norketamine were determined by enantioselective capillary electrophoresis. A two-phase model based on Hill kinetics was used to analyze the biotransformation of R/S-ketamine into R/S-norketamine and,...
Stewart AJ, Pettigrew A, Cochran AM, Belknap JK.The liver and lung are not only described as "target organs" in sepsis in most species, but are purported to be sources of circulating inflammatory mediators central to the systemic inflammatory response syndrome (SIRS). As we have recently reported an inflammatory response in the laminar tissue in laminitis similar to that described in "target organs" in human sepsis, we investigated the inflammatory response of the lung and liver in the black walnut extract (BWE) model of equine laminitis to determine (1) if a similar systemic inflammatory response occurs in this laminitis model as described...
Polkes AC, Giguère S, Lester GD, Bain FT.Neonatal foals with isoerythrolysis (NI) often die, but the risk factors for death have not been identified. Objective: To identify factors associated with outcome in foals with NI and to identify factors associated with death from liver failure or kernicterus in the same population. Methods: Seventy-two foals with NI examined at referral institutions. Methods: Retrospective case series. Information on signalment, clinical examination findings, laboratory testing, treatment, complications, outcome, and necropsy results were obtained. Results: The overall survival rate was 75% (54 of 72). Liver...
Moore RE, Knottenbelt D, Matthews JB, Beynon RJ, Whitfield PD.Ingestion of the poisonous weed ragwort (Senecio jacobea) by horses leads to irreversible liver damage. The principal toxins of ragwort are the pyrrolizidine alkaloids that are rapidly metabolised to highly reactive and cytotoxic pyrroles, which can escape into the circulation and bind to proteins. In this study a non-invasive in vitro model system has been developed to investigate whether pyrrole toxins induce specific modifications of equine blood proteins that are detectable by proteomic methods. Results: One dimensional gel electrophoresis revealed a significant alteration in the equine pl...
Axon JE, Russell CM, Begg AP, Adkins AR.A 10-month-old Thoroughbred filly was presented with a 2-month history of recurrent fever and pleural effusion. Major clinical findings were pyrexia and congested mucous membranes. Clinical pathology tests revealed an erythrocytosis, hyperfibrinogenaemia and hyperglobulinaemia. Pleural fluid was seen on ultrasonographic examination of the thorax and analysis of a thoracocentesis sample indicated a lymphocytic, modified transudate. A transtracheal aspirate was normal. The erythrocytosis persisted despite IV fluid therapy. Arterial blood gas analysis and bone marrow aspirate were normal. These f...
Szeredi L, Jánosi S, Tenk M.Klebsiella (K.) oxytoca infection induced the abortion of a female equine fetus in the 10th month of pregnancy. Bacteria were cultured from the liver, lung and stomach content. They were labelled with an anti-Mycobacterium bovis antibody in the thymus, liver and lungs and were stained with Giemsa and Brown-Brenn staining in the thymus and lung. The diffusely consolidated lungs contained numerous grey-whitish foci 2-4 mm in diameter, which corresponded to severe pyogranulomatous pneumonia characterised by numerous intraalveolar neutrophils and macrophages and multinucleated Langhans' giant cell...
DiMaio Knych HK, Stanley SD.Members of the CYP2D family constitute only about 2-4% of total hepatic CYP450s, however, they are responsible for the metabolism of 20-25% of commonly prescribed therapeutic compounds. CYP2D enzymes have been identified in a number of different species. However, vast differences in the metabolic activity of these enzymes have been well documented. In the horse, the presence of a member of the CYP2D family has been suggested from studies with equine liver microsomes, however its presence has not been definitively proven. In this study a cDNA encoding a novel CYP2D enzyme (CYP2D50) was cloned f...
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...
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...
