Experimentally induced cholangiohepatopathy by dosing sheep with fractionated extracts from Brachiaria decumbens.

Cholangiohepatopathy was induced in 5 lambs by oral administration of extracts from signal grass (Brachiaria decumbens) in Brazil. Grossly there were pale foci multifocally distributed throughout the hepatic parenchyma in 4 lambs. The microscopic changes, which were similar to those produced by other steroidal sapogenins-containing plants such as Tribulus terrestris and Panicum spp., included multifocal cholangitis, bile duct proliferation, and the presence of crystals in the biliary system.     

Crystal-associated cholangiohepatopathy and photosensitisation in lambs

Four outbreaks of hepatogenous photosensitisation occurred in weaned lambs in north eastern Victoria during the summers of 1985 and 1986. Attack rates varied between 7% and 43% and case fatality rates between 60% and 71%. Clinical signs included photosensitisation and jaundice. Serum biochemistry suggested hepatobiliary and hepatoparenchymal damage with impaired renal function. At necropsy livers were an ochre colour and kidneys a mottled brown to khaki. Histopathologically, needle-shaped to lenticular clefts were observed in and around bile ducts and in hepatocytes, hepatic sinusoidal macrophages and renal tubules. Optically active rhomboidal crystals were present in bile sediments. Panicum schinzii was identified as a possible cause in 2 of the 4 outbreaks. The clinical disease was reproduced in 2 of 6 lambs grazed on a toxic paddock. The disease was indistinguishable from geeldikkop except for the fact that Tribulus terrestris was not present on any of the 4 farms.     

Photosenitization of sheep on kleingrass pasture

The clinical appearance and serum gamma-glutamyl transpeptidase (GGT) activity were studied in 5 groups of sheep (12 per group) on kleingrass (Panicum coloratum) pasture plots and in 1 group of sheep (10 animals) on native buffalograss (Buchlo? dactyloides) pasture. Eleven sheep (at least 1 from each group on kleingrass pasture plots) had elevated serum GGT activity. Seven of 11 sheep with elevated serum GGT activity developed signs of photosensitization. None of the sheep on buffalograss pasture developed signs of photosensitization or elevated GGT activity. The pathologic findings were similar in the sheep that had signs of photosensitization. Grossly, there was icterus and subcutaneous edema. The livers had tapeworms (Thysanosoma actinioides) in the bile ducts, were slightly swollen, and varied in color from yellow to ochre in severe cases of biliary system derangements. Microscopically, there was cholangitis.     

Clinical and pathologic features of acute bovine liver disease in Australia

Acute bovine liver disease (ABLD) is a sporadic hepatic disease affecting cattle in southern Australia, characterized histologically by striking periportal hepatocellular necrosis. The cause of ABLD is unknown; however, the seasonality and acute presentation of outbreaks suggest mycotoxin involvement. We describe here the clinical and pathologic findings of ABLD in 45 naturally affected cattle from 13 outbreaks occurring from 2010 to 2019 in Victoria, Australia. Outbreaks occurred in herds located along the southern coastal plain of Victoria and were observed most frequently in lactating dairy cattle. Clinical signs commonly included a combination of mild photosensitization, progressive neurologic signs, and hypogalactia, which preceded death by ≤ 48 h. All affected animals had marked elevations in activities of glutamate dehydrogenase, aspartate aminotransferase, and gamma-glutamyl transferase. At autopsy, the most common lesions were serosal petechiae and/or gastrointestinal hemorrhage, and hepatomegaly with a pronounced hepatic reticular pattern. The principal histologic lesion was widespread—severe periportal hepatocellular coagulative necrosis and erythrocyte pooling—which often extended to massive necrosis. Lesions in other organs were uncommon. Our study of ABLD suggests involvement of a potent hepatotoxin that is either directly cytopathic or requires bioactivation by periportal-specific enzymes.     

Accumulation of 2,8 dihydroxyadenine in bovine liver, kidneys, and lymph nodes

A variety of tissues from 20 cattle slaughtered at federally inspected facilities contained abundant light green to greenish-yellow material. Gross lesions were most common in the liver and hepatic lymph nodes. Less frequent lesions were present in the mediastinal, renal, intercostal, and gastric lymph nodes. The material was most prominent in the portal triads, and in the medullary sinuses of the lymph nodes, at times occupying up to one half of the nodal mass. Renal calculi were present in one animal. Histologically, the condition was characterized by the intracytoplasmic accumulation of innumerable brown, acicular crystals in hepatocytes, macrophages, and renal tubular epithelial cells. Less frequent large aggregates of extracellular crystals were found in the lumens of renal tubules and in portal triads. Crystals were highly birefringent when examined using polarized light. The crystals were identified as 2,8 dihydroxyadenine using X-ray diffraction, electron diffraction, infrared spectroscopy, and mass spectrometry. In mammals, adenine is normally converted to adenylate by the enzyme adenine phosphoribosyltransferase. When adenine phosphoribosyltransferase is absent, deficient, or inhibited, adenine is oxidized to 2,8 dihydroxyadenine, which is extremely insoluble at physiological pH. In human beings, an autosomal recessive disease known as 2,8 dihydroxyadeninuria is caused by a deficiency of adenine phosphoribosyltransferase.     

紫菀不同极性段提取物对SD大鼠亚慢性毒性试验研究

本试验旨在观察紫菀不同极性段提取物对SD大鼠的肝脏毒性损伤。SD大鼠随机分为空白组、石油醚组、乙酸乙酯组、正丁醇组、母液组、75%乙醇组,每组10只,灌胃给药0.34g生药/kg体重,连续28 d,观察对大鼠摄食量、体增重、脏器系数、尿液指标、血常规、血清生化指标、肝脏组织抗氧化酶、病理切片等的影响。试验结果显示各组大鼠体增重、肝脏组织抗氧化酶、尿液指标、脏器系数均无显著变化(P>0.05);雄鼠乙酸乙酯组、母液组白细胞计数(WBC)显著降低(P<0.05),正丁醇组极显著降低(P<0.01),雌鼠石油醚组、乙酸乙酯组WBC极显著降低(P<0.01),正丁醇组显著降低(P<0.05);雌鼠乙酸乙酯组乳酸脱氢酶(LDH)显著升高(P<0.05);病理组织学检查可见石油醚组和乙酸乙酯组大鼠肝脏出现轻微的肝索紊乱、颗粒变性,其余组与空白组相比无明显差异。结果表明在0.34g生药/kg体重给药条件下,紫菀的石油醚和乙酸乙酯提取物对大鼠产生轻微的肝脏毒性。     

Study on Subchronic Toxicity Test of Different Polarity Section Extracts from Aster tataricus L.f.on SD rats

The aim of the experiment was to observe the liver toxicity of different polarity section extracts from Aster tataricus L.f.on SD rats.The subchronic test was performed via the daily oral administration of Aster tataricus L.f.at dose of 0.34 g/kg body weight in SD rats which were divided into six groups(control group, petroleum ether group, ethyl acetate group, N-butyl alcohol group, mother liquid group and 75% ethanol group), observing the effects on food consumption, body weight gain, viscera coefficient, urine examination, blood routine examination, serum biochemistry indices, liver antioxidant function analysis and histopathological observation.There was no significant changes of body weight gain, viscera coefficient, urine examination and liver antioxidant function among six groups(P>0.05), but WBC significantly and extremely significantly decreased in male rats of ethyl acetate group, mother liquid group and N-butyl alcohol group(P<0.05; P<0.01), and significantly and extremely significantly decreased in female rats of N-butyl alcohol group and petroleum ether group, ethyl acetate group(P<0.05; P<0.01);The LDH significantly increased in female rats of ethyl acetate group(P<0.05);Slight congestion and necrosis were showed in liver in petroleum ether group and ethyl acetate group, there was no differences observed in other groups.The extracts of Aster tataricus L.f., especially petroleum ether extract and ethyl acetate extract could cause slight liver toxicity under the dose of 0.34 g/kg body weight.     

Photosensitisation and crystal-associated cholangiohepatopathy in sheep grazing Brachiaria decumbens

Two outbreaks of photosensitivity and jaundice in sheep grazing the grass, Brachiaria decumbens. In West Java in 1983 and 1983 and 1990 are described. Aggregates of acicular clefts and crystals were present in bile canaliculi, bile ducts, Kupffer cells, hepatocytes and in kidney tubules. The number of crystals increased with the length of exposure to the plant and sheep that died had the largest accumulations. These crystalline structures have been reported before in this syndrome, but are similar to those seen in Tribulus terrestris and Panicum spp toxicities.     

Photosensitivity in South Africa. VI. The experimental induction of geeldikkop in sheep with crude steroidal saponins from Tribulus terrestris

Geeldikkop was induced in sheep by the oral administration of crude steroidal saponins from Tribulus terrestris. Two of the sheep developed typical lesions of geeldikkop, including birefringent crystalloid material in bile ducts and concentric periductal lamellar fibrosis. The clinical pathological changes in these sheep were also consistent with those of geeldikkop: aspartate transaminase and gamma-glutamyl transferase activities in the sera of both were elevated, and one had bilirubinaemia. A third sheep became photosensitive without typical lesions of geeldikkop in the liver or changes in the activities of liver enzymes before euthanasia. The findings of these trials are consistent with reports from abroad that ovine hepatogenous photosensitization, caused by Agave lechuguilla and Narthecium ossifragum, can be induced with crude saponins from the respective plants.     

Hepatogenous photosensitization associated with liver copper accumulation in buffalos

Four 1.5-year-old, male, Murrah buffalos were maintained during eight months without direct solar exposure during a study of copper toxicosis. Four days after solar exposure, all buffalos presented clinical manifestations consistent with acute photosensitization, including anorexia, apathy, loss of body weight, and generalized cutaneous lesions. Gross lesions were characterized by severe erythema, localized edema, fissures, tissue necrosis, gangrene and crust formation with serous exudation. Liver copper concentration was evaluated, and cutaneous biopsies were taken when clinical signs were evident. The liver copper concentration before solar exposure was increased in all animals. Histopathologic examination of the skin revealed hepatogenous photosensitization characterized by parakeratotic hyperkeratosis, acantholysis, degeneration of squamous epithelial cells, epidermal necrosis with atrophy of sweat glands, and multifocal superficial and deep dermal edema. These findings suggest that asymptomatic accumulation of copper within the liver might have induced hepatic insufficiency thereby resulting in secondary photosensitization when these buffalos were exposed to sunlight.     

Fall panicum (Panicum dichotomiflorum) hepatotoxicosis in horses and sheep

BACKGROUND: Fourteen horses at a boarding stable in Virginia were diagnosed with hepatic disease and locally grown hay was implicated as the cause. HYPOTHESIS: Panicum dichotomiflorum, the predominant grass species in the hay, is hepatotoxic to horses. ANIMALS: 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 trials were not blinded and no treatments were provided. Blood and liver specimens were collected and analyzed throughout the trials. RESULTS: Five affected animals were euthanized, whereas the others recovered. One research horse was euthanized for postmortem examination, and the other research animals recovered after hay withdrawal. All affected animals had evidence of hepatic disease with abnormally high aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP) activity. Evaluation of liver biopsy specimens disclosed mild lymphocytic and histiocytic inflammation, mild vacuolar change (hydropic degeneration), prominently clumped chromatin, and necrosis of individual hepatocytes. CONCLUSIONS AND CLINICAL IMPORTANCE: Severe hepatotoxicosis developed rapidly after Panicum hay exposure. Patchy hepatocyte necrosis was observed, implicating apoptosis as the mechanism of hepatotoxicosis. Absence of fibrosis in the research animals indicates that immediate withdrawal of Panicum hay should allow all but severely affected animals to recover from acute exposure.     

Crystal-associated cholangiopathy associated with the ingestion of Panicum spp. and other plants

Several panicoid grasses and some other plants throughout the world have been associated with a crystal-associated hepatopathy causing photosensitisation in ruminants. We have prepared sheep with reentrant bile duct cannulae and fed them on Panicum dichotomiflorum from the Waikato region. Bile from these sheep has been collected and crystals harvested by centrifugation and Percol density gradient techniques. These sheep, when slaughtered after showing elevations of serum bilirubin and enzymes indicating liver injury, had the typical cholangiohepatopathy of Panicum spp. toxicity. The crystals have now been identified as calcium salts of epismilagenin glucuronide. Likely precursor saponins of the sapogenin have been identified in Panicum dichotomiflorum. While we regard these findings as an important step forward in the understanding of these diseases, we are now investigating the factors, including known hepatotoxins, responsible for the occurrence of these hepatopathies.     

Experimental biliary cryptosporidiosis in broiler chickens

Biliary cryptosporidiosis was studied by inoculation of 2 x 10(5) Cryptosporidium baileyi oocysts (AU-B1 isolate) into the gall bladders of ten 6-day-old broiler chickens. Clinical signs of disease were not seen. Three of the 10 chickens developed biliary tract infections, based on histologic examination of tissue sections. Lesions seen in the gall bladders of these birds included epithelial hyperplasia and infiltration of the underlying connective tissue with mononuclear leukocytes. One of these birds also had involvement of the hepatic bile ducts. The bile ducts were mildly dilated and contained lesions similar to those seen in the gall bladder. Few to many cryptosporidia were present in the gall bladders and bile ducts of infected birds. Chickens may be of use in the study of biliary cryptosporidiosis, a common sequel to enteric infection in humans with human immunodeficiency virus infection.     

Hepatic enzyme changes in bovine hepatogenous photosensitivity caused by water-damaged alfalfa hay

In the winter of 1983, practitioners reported extensive photosensitization in 7 herds of cattle. All herds had a history of having been fed water-damaged alfalfa hay. A cow from one herd was referred to the veterinary teaching hospital at Oklahoma State University. In this herd of approximately 40 adult Polled Herefords, all cattle had had some degree of clinical involvement over the past 4 to 6 weeks. Clinical signs included scaling and erythema of sparsely haired skin, muzzle, and teats, as well as icterus, anorexia, and weight loss. One cow died, and the remaining cattle recovered over an 8- to 10-week period after removal of the hay from the ration. In the referred cow, values for total and conjugated bilirubin, BUN, creatinine, sorbitol dehydrogenase, serum alkaline phosphatase, serum aspartate transaminase, and serum gamma-glutamyl transferase were higher than normal. In the herd of origin, extremely high serum gamma-glutamyl transferase values (180 to 1,400 IU/L) persisted (normal, 2 to 35 IU/L). Feeding the same alfalfa hay to 2 clinically normal cows reproduced the syndrome. The characteristic hepatic lesion was bile duct necrosis, with secondary bile duct hyperplasia.     

Hepatitis and copper accumulation in Skye terriers

Livers of nine related Skye terriers with liver disease were evaluated for histological changes and copper content. Lesions ranged from hepatocellular degeneration and necrosis (zone 3) with intracanalicular cholestasis and mild inflammation, to chronic hepatitis with cholangioplasia and cirrhosis. Excess copper (801-2,257 micrograms/g) was related to the severity of cholestasis. Skye terrier hepatitis is a distinct disease entity and may be derived from a disorder of intracellular bile metabolism culminating in disturbed bile secretion and the accumulation of copper.     

Evaluation of total plasma bile acid concentrations for the diagnosis of hepatobiliary disease in horses

Plasma bile acid concentrations were measured in normal horses. There was no diurnal variation in values, and age and sex had no effect. There was no significant difference between serum and plasma bile acid concentrations in clinically normal horses. Plasma bile acids were stable on storage for one month at -20 degrees C. The total plasma bile acid concentrations together with total and direct bilirubin concentrations and plasma activities of aspartate aminotransferase, glutamate and iditol dehydrogenase were evaluated in horses with various types of hepatobiliary disease (hepatic necrosis, lipidosis, neoplasia and cirrhosis), gastrointestinal disease, cardiovascular, orthopaedic and various other conditions not affecting the liver. Total plasma bile acids together with plasma glutamate and iditol dehydrogenase activities were the best indicators of liver disease. Total plasma bile acid concentrations were the most sensitive indicator of a wide variety of hepatic diseases but alone were unhelpful in differential diagnosis and were of more value when combined with the other tests of hepatic disease.     

Glycogen accumulation and histological changes in the livers of lambs with alveld and experimental sporidesmin intoxication

Alveld is a hepatogenous photosensitization disease seen in lambs grazing Narthecium ossifragum pastures in Norway. Mycotoxins, possibly sporidesmin, have been suspected to cause the liver damage in alveld as in facial eczema. The histological changes in the liver of alveld cases and in lambs photosensitized after experimental sporidesmin intoxication were compared. The liver damage characterized by necrosis in single centrilobular hepatocytes, was of the same type in both conditions. Minor to moderate portal fibroplasia and bile duct proliferation were almost always present. Accumulated glycogen was seen in hepatocytes in the centrilobular areas. This was significantly correlated to the enzymatically measured glycogen content and there was good correlation between parenchymal damage and glycogen accumulation. The glucose-6-phosphatase and glycogen phosphorylase activities were normal. These findings indicate that parenchymal damage, rather than obstruction of the bile ducts, caused the retention of phylloerythrin both in alveld cases and in experimentally sporidesmin-intoxicated lambs. The accumulation of glycogen could not be explained.Abbreviations HE haematoxylin and eoson - PAS periodic acid Schiff - EDTA ethylene diamine tetracetic acid     

Alterations in selected serum biochemical constituents in equids after induced hepatic disease

Effects of induced cholestasis and hepatocellular necrosis and of fasting on serum biochemical constituents including bile acids, IgA, bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), arginase, and the clearance of sodium sulfobromophthalein were studied in 4 groups of equids. The reference value for serum bile acids, as determined by an enzymatic colorimetric procedure for horses and ponies was 5.94 +/- 2.72 mumol/L, there being no statistical difference for horses and ponies. Sample collection at time of feeding had no effect on serum bile acid concentration. Seemingly, serum bile acids, arginase, and GGT were the most sensitive indicators of cholestasis and/or hepatocellular necrosis and would form an essential minimum effective battery of tests to diagnose and prognose hepatic disease in equids. These tests provided a measure of hepatobiliary transport function (bile acids), cell necrosis (arginase), and cholestasis (GGT and bile acids).     

Changes in plasma bile acids,plasma amino acids,and hepatic enzyme pools as indices of functional impairment in liver-damaged sheep

Plasma bile acids, plasma amino acids, and the total hepatic pools of aspartate aminotransferase, gamma glutamyltransferase, glutamate dehydrogenase, and sorbitol dehydrogenase were compared in control sheep (Group 1), sheep with subclinical pyrrolizidine alkaloid toxicosis (Group 2), and in sheep with acute hepatocellular necrosis associated with the hemolytic phase of chronic copper poisoning (Group 3). Subclinical pyrrolizidine alkaloid toxicosis was not associated with any changes in bile acid or amino acid status but was associated with a significant decline in the hepatic pools of sorbitol dehydrogenase and aspartate aminotransferase. This observation could not be explained in terms of enzyme leakage from damaged hepatocytes and suggested that pyrrolizidine alkaloids might specifically inhibit hepatocellular enzyme synthesis. Group 3 sheep also had reduced hepatic enzyme pools which were at least partly referable to enzyme leakage from damaged hepatocytes. In these sheep, increases in plasma bile acids were a more sensitive index of hepatic function than were either increased aromatic amino acid concentration or the ratio between branched chain and aromatic amino acids.     

Bile acid concentrations in the diagnosis of hepatobiliary disease in the dog

The clinical usefulness of measuring serum bile acid concentrations as a diagnostic test for hepatobiliary disease, was examined in 150 dogs that were suspected of having hepatic disease. Serum values of total bilirubin (TB), alkaline phosphatase (ALP), alanine transaminase (ALT), and albumin were also measured. Fasting serum bile acid (FSBA) values were determined, using a solid-phase radioimmunoassay for total conjugated bile acids or a direct enzymatic spectrophotometric method. A definitive diagnosis was established by histologic examination of the liver. On the basis of histologic findings, dogs were assigned to groups (1 to 8, respectively) including: extrahepatic bile duct obstruction, cirrhosis, portal systemic vascular anastomosis (PSVA), hepatic necrosis, intrahepatic cholestasis, steroid hepatopathy, neoplasia, and secondary disease. Dogs in group 8 had no morphologic evidence of hepatobiliary disease or had mild hepatic lesions. Test efficacies of FSBA, TB, ALP, ALT, and albumin were expressed using 4 indices: sensitivity, specificity, and positive-predictive and negative-predictive values. The diagnostic efficacy of FSBA was examined alone and in combinations with the other tests. There was wide overlapping of FSBA values among dogs in groups 1 to 7, and there was wide overlapping of ALT and ALP values among dogs in all groups. The specificity of FSBA for the diagnosis of liver disease exceeded 90% at values greater than or equal to 30 mumol/L and reached 100% at greater than or equal to 50 mumol/L. Individual liver tests with the best sensitivity for each group were:FSBA and ALP for extrahepatic bile duct obstruction; FSBA for cirrhosis and PSVA; ALT for hepatic necrosis; and ALP for intrahepatic cholestasis, steroid hepatopathy, and neoplasia. Combinations of tests with the best sensitivity for each group were: FSBA + ALP for extrahepatic bile duct obstruction; FSBA + ALT for cirrhosis and PSVA; FSBA + ALT and TB + ALT for hepatic necrosis; and FSBA + ALP for intrahepatic cholestasis, steroid hepatopathy, and neoplasia. Individual tests had the best sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)