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Topic:Hepatic Function
Hepatic function in horses involves the liver's role in various physiological processes, including metabolism, detoxification, and the synthesis of essential proteins and bile. The liver is responsible for processing nutrients absorbed from the digestive tract, converting them into energy, and storing them for future use. It also plays a vital role in detoxifying the blood by metabolizing drugs and toxins. Additionally, the liver synthesizes proteins necessary for blood clotting and immune function, as well as producing bile to aid in the digestion and absorption of fats. This page aggregates peer-reviewed research studies and scholarly articles that explore the liver's functions, its regulation, and its impact on equine health.
Hepatic Dicrocoelium dendriticum infection in a miniature horse. A miniature horse which died following humane seizure from an Ontario farm was emaciated with serous atrophy of fat. Autopsy revealed hepatic atrophy and moderate periportal fibrosis. Eggs and trematodes seen in the liver were identified as Dicrocoelium dendriticum. This appears to be the first reported case of infection of equids in North America with Dicrocoelium dendriticum. Infection parDicrocoelium dendriticumhépatique chez un cheval miniature. Un cheval miniature qui est mort à la suite d’une saisie humanitaire dans une ferme de l’Ontario était émacié et avait une atrophie sére...
Congenital Hepatic Fibrosis in a Purebred Spanish Horse Foal: Pathology and Genetic Studies on PKHD1 Gene Mutations. A 1-month-old Purebred Spanish Horse (PSH) foal presented with progressive hepatic failure culminating in death. Hepatic lesions were consistent with congenital hepatic fibrosis (CHF). Genetic studies in the PKHD1 gene in the affected foal revealed that it was heterozygous for the 2 previously described single-nucleotide polymorphisms (SNPs) linked to CHF in Swiss Franches-Montagnes (SFM) horses. In addition, 2 novel mutations were detected, the foal being homozygous for one of them and heterozygous for the other. Genetic studies in a healthy PSH population ( n = 35) showed a 3-fold higher gen...
Intestinal and hepatic contributions to the pharmacokinetic interaction between gamithromycin and rifampicin after single-dose and multiple-dose administration in healthy foals. Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative. Objective: To evaluate the pharmacokinetic ...
The effects of aging on hepatic microsomal scaling factor and hepatocellularity number in the horse. 1. Scaling factor values for the in vitro-in vivo extrapolation of hepatic metabolic clearance for xenobiotics have not yet been determined in horses. Scaling factors were determined by comparing the total protein and or cytochrome (CYP) P450 content in microsomes and cryopreserved hepatocytes against the content in the liver. 2. Microsomal protein per gram of liver (MPPGL) and hepatocellularity number per gram of liver (HPGL) using CYP P450 content method ranged 41-73 mg/gram of liver (mean= 57 mg/gram of liver, n = 39) and 146-320 × 10 cells/g of liver (mean = 227× 10 c...
Acute hepatic steatosis: a helpful diagnostic feature in metallic phosphide-poisoned horses. Metal phosphides, particularly zinc and aluminum phosphide, occasionally poison horses and other equids following their use as rodenticides and insecticides. Grain-based aluminum phosphide baits are used to control rodents such as prairie dogs. The clinical course in intoxicated horses is short (24 h of clinical signs) had centrilobular hepatic necrosis with congestion and a mixture of microvesicular and macrovesicular steatosis. Phosphine poisoning should be considered in horses that die acutely and are found to have steatosis, either with or without hepatocellular necrosis.
Effect of feed deprivation on selected parameters of lipid mobilisation and hepatic function in healthy Akhal Teke horses. Gastrointestinal and other systemic diseases of Equidae are often characterised by partial or complete inappetence. The catabolic processes may lead to lipid mobilisation and other metabolic disturbances. Evidence from earlier studies has revealed that during feed deprivation/inappetence, the conjugation of bilirubin is reduced causing a substantial rise of the total bilirubin and its unconjugated fraction. Objective: We hypothesised that during feed deprivation, the serum concentration of free fatty acids (FFA), triglycerides (TG), blood urea nitrogen (BUN), total bilirubin (tBIL), total bile...
Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies. Despite reports of the successful isolation of primary equine hepatocytes, there are no published data regarding the successful cryopreservation of these isolated cells. In this study, a detailed description of the procedures for isolation, cryopreservation, and recovery of equine hepatocytes are presented. Furthermore, the intrinsic clearance (Cl) and production of metabolites for three drugs were compared between freshly isolated and recovered cryopreserved hepatocytes. Primary equine hepatocytes were isolated using a two-step collagenase perfusion method, with an average cell yield of 2.47Â...
Presumptive Iatrogenic Microcystin-Associated Liver Failure and Encephalopathy in a Holsteiner Gelding. An 8-year-old Holsteiner gelding was presented for evaluation of anorexia, obtundation, icterus, and mild colic signs of 48 hours duration. History, physical examination, and initial diagnostics were suggestive of hepatic disease and encephalopathy. Microcystin toxicosis was suspected based on historical administration of a cyanobacteria supplement, associated serum biochemistry abnormalities, and characteristic histopathological changes. Microcystin contamination was confirmed in both supplement containers fed to the horse. Fulminant hepatic failure and encephalopathy progressed resulting in ...
Rapid LC-MS/MS method for the determination of 4-hydroxycholesterol/cholesterol ratio in serum as endogenous biomarker for CYP3A activity in human and foals. Cytochrome P450 3A (CYP) enzymes are involved in the elimination of many drugs and are known to be regulated by several environmental factors. Thus, it was the aim of this study to develop and validate an analytical method allowing estimation of the hepatic CYP3A enzyme activity using the 4-hydroxycholesterol to cholesterol ratio as an endogenous biomarker in serum. Both compounds were isolated from the biological matrix by liquid-liquid extraction using n-hexane after saponification with ethanolic sodium methoxide solution (2M) to cleave the steroids from their esterified forms without any ki...
Equine Mesenchymal Stromal Cells from Different Sources Efficiently Differentiate into Hepatocyte-Like Cells. Adult equine hepatocytes have proven challenging to culture long term in vitro as they rapidly lose their morphology and functionality, thus limiting studies on liver function and response to disease. In this study, we describe for the first time the differentiation of equine mesenchymal stromal cells (MSC) from a variety of sources into functional hepatocyte-like cells (HLC). First, we differentiated equine umbilical cord blood (UCB)-derived MSC into HLC and found that these cells exhibited a distinct polygonal morphology, stored glycogen as visualized by periodic acid Schiff's reagent staini...
Chronic active interstitial pancreatitis as a cause of transverse colonic obstruction and colic in a horse. A mature Quarter horse was euthanized following colic of 3 days duration. Postmortem, the large intestine, except the descending colon, was diffusely distended and associated with adhesion of the transverse colon to the pancreas, which had changes consistent with chronic active interstitial pancreatitis. Other lesions included hepatic fibrosis, erosive gastritis, and bilateral adrenal cortical hyperplasia. Pancréatite interstitielle chronique active comme cause d’une obstruction du côlon transversal et de coliques chez un cheval. Un cheval Quarter horse adulte a été euthanasié après de...
Medical and surgical management of an intra-abdominal abscess of hepatic origin in a horse. A 4-year-old Arabian-cross mare was examined because of a 48-hour history of pyrexia, lethargy, and signs of abdominal discomfort. Results: On initial evaluation, the horse was in good body condition, but febrile, tachycardic, tachypneic, and icteric and had signs of colic. Findings on CBC and serum biochemical analysis indicated marked systemic inflammation and hepatocellular damage. Serial abdominal ultrasonographic examinations revealed progressive, localized hepatic parenchymal abnormalities in the left ventral aspect of the abdomen in proximity to the left liver lobes, and eventual identi...
Serum bile acid concentrations, histopathological features, and short-, and long-term survival in horses with hepatic disease. Serum bile acid concentrations (SBA) and a histopathological biopsy score [Equine Vet J 35 (2003) 534] are used prognostically in equine hepatic disease. Objective: Histopathologic features and scores, but not SBA, differ between survivors and nonsurvivors and correlate with histopathologic evidence of hepatic inflammation and fibrosis. Methods: Retrospective study. Records (1999-2011) of horses with hepatic disease diagnosed by biopsy and with concurrent measurements of SBA. Methods: Retrospective cohort study. Biopsies were examined for inflammatory cell infiltration including type and distr...
Congenital hepatic fibrosis in the Franches-Montagnes horse is associated with the polycystic kidney and hepatic disease 1 (PKHD1) gene. Congenital hepatic fibrosis has been described as a lethal disease with monogenic autosomal recessive inheritance in the Swiss Franches-Montagnes horse breed. We performed a genome-wide association study with 5 cases and 12 controls and detected an association on chromosome 20. Subsequent homozygosity mapping defined a critical interval of 952 kb harboring 10 annotated genes and loci including the polycystic kidney and hepatic disease 1 (autosomal recessive) gene (PKHD1). PKHD1 represents an excellent functional candidate as variants in this gene were identified in human patients with autosoma...
Evaluation of a copro-antigen ELISA to detect Fasciola hepatica infection in sheep, cattle and horses. To determine the specificity and sensitivity of a commercial copro-antigen ELISA for the detection of Fasciola hepatica infection in cattle and sheep and to assess the suitability of the test for use in horses. Methods: Testing was done on more than 100 negative faecal samples from each of sheep, cattle and horses and on at least 40 positive faecal samples from each species. Positive samples were selected based on a positive sedimentation test for liver fluke eggs. Faecal samples of animals from Western Australia, which is free of liver fluke infection, served as negative controls. Specificity...
The pharmacokinetics of glycopyrrolate in Standardbred horses. The disposition of plasma glycopyrrolate (GLY) is characterized by a three-compartment pharmacokinetic model after a 1-mg bolus intravenous dose to Standardbred horses. The median (range) plasma clearance (Clp), volume of distribution of the central compartment (V1 ), volume of distribution at steady-state (Vss), and area under the plasma concentration-time curve (AUC0-inf ) were 16.7 (13.6-21.7)Â mL/min/kg, 0.167 (0.103-0.215)Â L/kg, 3.69 (0.640-38.73)Â L/kg, and 2.58 (2.28-2.88)Â ng*h/mL, respectively. Renal clearance of GLY was characterized by a median (range) of 2.65 (1.92-3.59)Â mL/min/k...
Induction of cytochrome P450 enzymes in primary equine hepatocyte culture. In this study, we established cell culture conditions for primary equine hepatocytes allowing cytochrome P450 enzyme (CYP) induction experiments. Hepatocytes were isolated after a modified method of Bakala et al. (2003) and cultivated on collagen I coated plates. Three different media were compared for their influence on morphology, viability and CYP activity of the hepatocytes. CYP activity was evaluated with the fluorescent substrate 7-benzyloxy-4-trifluoromethylcoumarin. Induction experiments were carried out with rifampicin, dexamethasone or phenobarbital. Concentration-response curves for...
Severe hypertriglyceridaemia in horses and ponies with endocrine disorders. Severe hypertriglyceridaemia in horses and ponies with endocrine disorders has been reported anecdotally but has not been documented in the literature. Objective: To describe historical and clinicopathological findings as well as progression and outcome in horses and ponies with severe hypertriglyceridaemia (serum triglyceride concentration >5.65 mmol/l) secondary to an endocrine disorder that were otherwise apparently healthy. Methods: Cases from 6 participating institutions were identified and case details extracted from the medical records. Results: Case details of 3 horses and 4 ponies ...
Diagnostic exercise: poor performance in a racehorse. A 9-year-old Thoroughbred gelding presented with a 97-day history of poor performance and intermittent fever. Clinicopathologic changes included increased serum activity of γ-glutamyltransferase and alkaline phosphatase, mild hyperbilirubinemia, and leukocytosis with neutrophilia and lymphopenia. Abdominal ultrasound revealed hepatomegaly with hyperechoic hepatic parenchyma and biliary distention. Pathologic findings included marked hepatomegaly (liver 3.6% of body weight), firm hepatic consistency with a diffuse enhanced reticular pattern, severe portal bridging and sinusoidal fibrosis, oval...
Pathological evidence of pancreatitis in 43 horses (1986-2011). Definitive ante mortem diagnosis of pancreatitis in horses is difficult. Reports summarising the most common clinical signs, clinicopathological features and concurrent disorders in horses with a definitive diagnosis of pancreatitis that may aid in the recognition of disease are lacking. Objective: To describe case details, clinical signs, clinicopathological data and necropsy findings in horses with a definitive diagnosis of pancreatitis. Methods: This was a retrospective study (1986-2011) and inclusion criteria consisted of horses with a definitive diagnosis of pancreatitis. A medical record...
Hepatoencephalopathy syndrome due to Cassia occidentalis (Leguminosae, Caesalpinioideae) seed ingestion in horses. 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...
Copper-associated hepatic cirrhosis in a Friesian horse. A 6-year-old Friesian stallion was examined because of signs of exercise intolerance, stiff gait and symmetrical hind weakness, and increased serum liver enzymes. On presentation, the horse showed muscle atrophy of the hindquarters. Neurological investigation showed no abnormalities. Laboratory findings revealed a prolonged prothrombin time and increased levels of alkaline phosphatase (AF), aspartate aminotransferase (ASAT), gamma-glutamyl-transferase (GGT), lactate dehydrogenase (LDH), and bile acids. Histological evaluation of the liver revealed severe cirrhosis and intracytoplasmic greyish ...
Acute and long-term cardiomyopathy and delayed neurotoxicity after accidental lasalocid poisoning in horses. Horses are extremely susceptible to ionophore intoxication. Although numerous reports are available regarding monensin, little is known about lasalocid toxicity. Objective: To describe accidental lasalocid poisoning on a farm in Belgium. Methods: Eighty-one horses, of which 14 demonstrated clinical signs from day 0-21 after being fed a new concentrate batch. One horse died on day 20 and another on day 27. Methods: The most severe cases (n = 7), admitted to the clinic on day 29-46, underwent cardiac examination and blood biochemical analysis, including determination of plasma cardiac troponin...
Heterobilharzia americana infection as a cause of hepatic parasitic granulomas in a horse. CASE DESCRIPTION-A 22-year-old American Paint Horse gelding from the Gulf Coast region of Texas was evaluated for regrowth of a perirectal squamous cell carcinoma that had been surgically removed 11 months previously. CLINICAL FINDINGS-A necrotic and ulcerated mass was present below the anus. The horse had paraphimosis and was having difficulty with urination. Histologic examination of the mass revealed that it was squamous cell carcinoma, and the horse was euthanized because of the unlikelihood that the mass could be adequately resected and its close proximity to the urethra. OUTCOME-At necro...
Serum amyloid A is expressed in histologically normal tissues from horses and cattle. mRNA expression of the acute phase protein serum amyloid A (SAA) in histologically normal tissues derived from horses (n=13) and cattle (n=4) was investigated by quantitative reverse-transcriptase real-time polymerase-chain reaction. As expected, high constitutive SAA mRNA expression was demonstrated in hepatic tissue in both species. In horses, moderate (>1% of the hepatic expression) SAA mRNA expression was detected in the lung, mammary gland, pancreas, synovial membrane, thymus, thyroid gland and uterus. Other equine tissues and organs sampled included adipose tissue, adrenal gland, aort...
Hepatic and metabolic changes in surgical colic patients: a pilot study. To determine: (1) changes in blood ammonia, bile acid (BA), bilirubin, triglyceride, and glucose concentrations and liver enzyme activities in perioperative colic patients and (2) the association between these laboratory findings and short-term survival. Methods: Prospective observational clinical study. Methods: Thirty-two adult horses undergoing exploratory celiotomy for colic. Methods: None. Results: Blood samples were collected preoperatively and at 24-36 and 72-84 hours postoperatively and analyzed for blood ammonia, BA, bilirubin, triglyceride, and glucose concentrations and sorbitol deh...
The effects of deferoxamine mesylate on iron elimination after blood transfusion in neonatal foals. Hepatic failure is one of the more common complications in foals requiring blood transfusion to treat neonatal isoerythrolysis. Iron intoxication is likely the cause of hepatic injury. Objective: To determine the effects of deferoxamine on iron elimination in normal foals. Methods: Thirteen neonatal foals. Methods: Randomized-controlled trial. At 1-3 days of age, foals received either 3 L of washed packed dam's red blood cells (RBC) or 3 L of saline IV once. Foals were treated with deferoxamine (1 g) or saline (5 mL) SC twice daily for 14 days. Foals were randomly assigned to 1 of 3 gr...
