Topic:Liver Function
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.
Uterine fibrosarcoma in a Warmblood mare. This paper describes a case of uterine fibrosarcoma in an 18-year-old Warmblood mare. The mare had exhibited bloody fluid accumulation inside the uterus and vaginal haemorrhagic discharge since the previous foaling. The mare was euthanized, and on pathological examination, in addition to the uterine neoplasia, multiple metastases were found in the lungs, liver and spleen. The histological and immunohistochemical examination determined that the tumour was a fibrosarcoma. To our knowledge, this is the first paper to describe a uterine fibrosarcoma in a mare.
Acute lameness associated with osseous metastasis of a peri-renal carcinoma in a horse. We present a case of aggressive metastatic carcinoma in a horse that was initially presented for shoulder lameness. Although radiography and scintigraphy were useful for localising a lesion in the proximal humerus, subsequent development of non-specific signs of systemic disease prompted further evaluation. Haematology and blood biochemistry, urinalysis and ultrasonography were all instrumental in identifying renal involvement. A diagnosis of a peri-renal mass causing secondary renal failure prompted euthanasia of the horse because of the poor prognosis. Antemortem findings were supported by n...
Evaluation of the positive predictive value of serum protein electrophoresis beta-gamma bridging for hepatic disease in three domestic animal species. Beta-gamma bridging (β-γ bridging) on serum protein electrophoresis is touted as being virtually pathognomonic for hepatic disease. However, the criteria for β-γ bridging are not defined, and few publications support a relationship between β-γ bridging and liver disease. The goal of this retrospective study was to evaluate the prevalence of hepatic pathology in animals with β-γ bridging. All serum protein electrophoretograms from clinical patients generated at the University of Georgia between 1994 and 2008 were evaluated for the presence of β-γ bridging, defined as (1) an albumin:gl...
Expression and localization of BCRP, MRP1 and MRP2 in intestines, liver and kidney in horse. 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...
A potential role for indoleamine 2,3-dioxygenase (IDO) in Rhodococcus equi infection. Rhodococcus equi is a facultative intracellular bacterial pathogen of foals and immunocompromised humans that infects and proliferates within host macrophages and dendritic cells (DC). Indoleamine 2,3-dioxygenase (IDO), the initial enzyme in the tryptophan catabolism pathway, is upregulated in R. equi infected equine monocyte-derived DC and alveolar macrophages. Tryptophan requirement of R. equi for extracellular and intracellular growth was assessed. Growth of R. equi in minimal media did not require tryptophan and pharmacologic inhibition of IDO had no effect on intracellular proliferation o...
Toxicological effects of aflatoxins in horses. Aflatoxins are a group of mycotoxins principally produced by Aspergillus flavus and A. parasiticus, which are both natural contaminants of food and feedstuff. Aflatoxin B(1) is the most prevalent member of this group that is normally detected and is the most powerful hepatocarcinogen known. Few naturally occurring episodes of aflatoxicosis in horses have been reported in the literature. Indeed, the published information about aflatoxin exposure, metabolism and the effects on horses is limited and controversial, possibly indicating a lack of awareness rather than the rarity of the occurrence. T...
Molecular cloning, expression, and initial characterization of members of the CYP3A family in horses. The use of performance-enhancing drugs in the horse racing industry combined with the need for more rational approaches in the use of therapeutic agents in equids necessitates additional studies on the spectrum, content, and catalytic activities of hepatic cytochrome P450 monooxygenases in this species. In this study, three cytochrome P450 (P450) monooxygenases in the 3A family were cloned from, sequenced, and expressed in a baculovirus expression system. The proteins were designated CYP3A89, CYP3A96, and CYP3A97. Expression studies produced various results among the three proteins. CYP3A89 ap...
Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses. The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same sur...
Equine primary liver tumors: a case series and review of the literature. Hepatoblastoma (HB) is an uncommon pediatric liver tumor in humans and horses. In humans, HB is most frequently diagnosed in fetuses, neonates, and young children, whereas hepatocellular carcinoma (HCC) affects juvenile and adult humans. Hepatoblastoma in the horse is rare, with only 9 reported cases. Affected horses ranged in age from late-term aborted fetuses to 3 years. The current study describes 3 new cases of primary liver tumors in horses and reviews findings in relation to other reports on this condition. Tumors classified as HB were identified in a male Standardbred aborted fetus and ...
De novo fatty acid synthesis and NADPH generation in equine adipose and liver tissue. The lipogenic capacities of equine liver and adipose tissue explants were investigated in vitro. Preference for glucose or acetate as the primary carbon source for de novo fatty acid synthesis was determined using (14)C labeled substrates. Additional aims included determining the relative contribution of NADPH generating pathways to reducing equivalent generation and comparing the lipogenic activity of two adipose depots, mesenteric and subcutaneous harvested from the crest region of the neck. Mesenteric adipose tissue had greater lipogenic activity than subcutaneous adipose tissue, and liver ...
Colic caused by Panicum maximum toxicosis in equidae in northern Brazil. In the Amazon region of northern Brazil, Panicum maximum cultivars Mombaça, Tanzânia, and Massai cause severe colic and death in horses and mules. The disease occurs in the rainy season, when sprouting pastures are grazed by equidae. In the 8 separate disease outbreaks studied, a total of 52 out of 153 equidae were affected, including 19 that died (10 mules and 9 horses). Clinical signs were colic and abdominal dilatation, with a clinical manifestation period of 12 hr to 4 days. Serum activities of gamma-glutamyl transferase and aspartate aminotransferase were within reference intervals; how...
In vitro and in vivo studies of androst-4-ene-3,6,17-trione in horses by gas chromatography-mass spectrometry. This paper describes the application of gas chromatography-mass spectrometry (GC-MS) for in vitro and in vivo studies of 6-OXO in horses, with a special aim to identify the most appropriate target metabolite to be monitored for controlling the administration of 6-OXO in racehorses. In vitro studies of 6-OXO were performed using horse liver microsomes. The major biotransformation observed was reduction of one keto group at the C3 or C6 positions. Three in vitro metabolites, namely 6alpha-hydroxyandrost-4-ene-3,17-dione (M1), 3alpha-hydroxyandrost-4-ene-6,17-dione (M2a) and 3beta-hydroxyandrost-...
Cloning, sequencing and expression analysis of the equine hepcidin gene by real-time PCR. Equine serum or plasma iron concentration drops quickly during inflammation. Accumulation of iron inside macrophages and reduction of the intestinal absorption of this element cause hypoferremia during systemic inflammatory processes. These mechanisms are mediated by hepcidin, a 25 amino acids peptide synthesized mainly in the liver in response to iron stores and inflammation. Hepcidin is an important peptide for systemic iron homeostasis and also has antibacterial and antifungal activities. Hepcidin up-regulation is particularly useful during acute inflammation, especially before adaptive imm...
The application of in vitro technologies to study the metabolism of the androgenic/anabolic steroid stanozolol in the equine. In this study, the use of equine liver/lung microsomes and S9 tissue fractions were used to study the metabolism of the androgenic/anabolic steroid stanozolol as an example of the potential of in vitro technologies in sports drug surveillance. In vitro incubates were analysed qualitatively alongside urine samples originating from in vivo stanozolol administrations using LC-MS on a high-resolution accurate mass Thermo Orbitrap Discovery instrument, by LC-MS/MS on an Applied Biosystems Sciex 5500 Q Trap and by GC-MS/MS on an Agilent 7000A. Using high-resolution accurate mass full scan analysis o...
Effects of fusariotoxins in the equine species. 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...
CE provides evidence of the stereoselective hydroxylation of norketamine in equines. 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 ...
In vitro evaluation of differences in phase 1 metabolism of ketamine and other analgesics among humans, horses, and dogs. 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...
Hepatic lobe torsion in a horse. 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...
P-glycoprotein in intestines, liver, kidney and lymphocytes in horse. 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...
Bilateral laryngeal paralysis associated with hepatic dysfunction and hepatic encephalopathy in six ponies and four horses. 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 ...
Perforation of the gastrointestinal tracts of four horses by metallic wires. 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.
Ocular and multicentric lymphoma in a young racehorse. 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. ...
Stereoselective biotransformation of ketamine in equine liver and lung microsomes. 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,...
Indices of inflammation in the lung and liver in the early stages of the black walnut extract model of equine laminitis. 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...
Factors associated with outcome in foals with neonatal isoerythrolysis (72 cases, 1988-2003). 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...
Biomarkers for ragwort poisoning in horses: identification of protein targets. 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...
Erythrocytosis and pleural effusion associated with a hepatoblastoma in a Thoroughbred yearling. 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...
Klebsiella oxytoca as a cause of equine abortion–short communication. 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...
Complementary DNA cloning, functional expression and characterization of a novel cytochrome P450, CYP2D50, from equine liver. 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...