atractyloside and Necrosis

In order to evaluate the susceptibility of sheep to V. rubricaulis and to establish the clinical signs, serum biochemistry, and pathological findings, eight sheep were fed varying doses of V. rubricaulis. The onset of clinical signs occurred 6-48 h after the ingestion of V. rubricaulis. Clinical courses lasted 6-56 h after the ingestion of the plant. Serum activities of aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase were highly elevated and glucose blood levels were low in affected sheep. Clinical signs consisted of apathy, anorexia, dry muzzle, respiratory distress, abdominal pain, and mushy feces with streaks of blood and mucus. Two sheep had neurological signs including muscle fasciculation, nystagmus, paddling movements, and blindness. Liver necrosis could be detected antemortem through liver biopsy. Five sheep died and three recovered. The liver was affected in all necropsied sheep; it increased in volume and had marked accentuation of the lobular pattern with red, depressed areas intercalated with a pale yellow network. Ascites and hydropericardium were consistent findings. Microscopically, centrilobular to massive coagulative necrosis was observed. Coagulative necrosis was also observed in a few proximal renal tubules. Microscopic lesions were not found in any other organs. The severity of liver lesions was proportional to the dose. Chemical analysis to detect carboxyatractyloside in V. rubricaulis plant material was negative. It is concluded that V. rubricaulis poisoning in sheep is clinically, biochemically, and pathologically characteristic of an acute hepatoxicosis.

Topics: Alkaline Phosphatase; Animals; Ascites; Aspartate Aminotransferases; Atractyloside; Blood Glucose; gamma-Glutamyltransferase; Liver; Necrosis; Plant Poisoning; Sheep; Sheep Diseases; Vernonia

Xanthium strumarium, commonly referred to as "cocklebur," rarely causes poisoning in cattle. When mature, this robust, annual weed bears numerous oval, brownish, spiny burs. Only the seeds in the burs and young seedlings (cotyledonary leaves) contain the toxic principle, carboxyatractyloside. In the Frankfort district of the Free State Province of South Africa, a herd of 150 Bonsmara cows were allowed to graze on the banks of a small river, where mature cocklebur was growing. Four cows died while grazing in this relatively small area. Clinical signs ranged from recumbency, apparent blindness, and hypersensitivity to convulsive seizures. During necropsy, burs completely matted with ingesta were located in the rumen content. The most distinctive microscopic lesions were severe, bridging centrilobular to midzonal hepatocyte necrosis and hemorrhage. Ultrastructurally, periacinar hepatocytes were necrotic, and novel electron-dense cytoplasmic needle-like crystals were observed, often in close association with peroxisomes. Carboxyatractyloside concentrations were determined using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Carboxyatractyloside was present in rumen contents at 2.5 mg/kg; in burs removed from the rumen at 0.17 mg/kg; in liver at 66 ng/g, and was below the limit of quantitation in the kidney sample, estimated at approximately 0.8 ng/g. Based on the presence of the plants on the riverbank, the history of exposure, the clinical findings, the presence of burs in the rumen, and the microscopic and ultrastructural lesions, X. strumarium poisoning in the herd of cattle was confirmed and was supported by LC-HRMS.

Topics: Animals; Atractyloside; Cattle; Cattle Diseases; Female; Gastrointestinal Contents; Kidney; Liver; Necrosis; Plants, Toxic; Rumen; Seeds; South Africa; Xanthium

Cocklebur (Xanthium strumarium) fed to feeder pigs was associated with acute to subacute hepatotoxicosis. Cotyledonary seedings fed at 0.75% to 3% of body weight or ground bur fed at 20% to 30% of the ration caused acute depression, convulsions, and death. Principle gross lesions were marked serofibrinous ascites, edema of the gallbladder wall, and lobular accentuation of the liver. Acute to subacute centrilobular hepatic necrosis was present microscopically. The previously reported toxic principle, hydroquinone, was not recovered from the plant or bur of X. strumarium. Authentic hydroquinone administered orally failed to produce lesions typical of cocklebur intoxication but did produce marked hyperglycemia. Carboxyatractyloside recovered from the aqueous extract of X. strumarium and authentic carboxyatractyloside, when fed to pigs, caused signs and lesions typical of cocklebur intoxication. Marked hypoglycemia and elevated serum glutamic oxaloacetic transaminase and serum isocitric dehydrogenase concentrations occurred in pigs with acute hepatic necrosis that had received either cocklebur seedlings, ground bur or carboxyatractyloside.

Topics: Animals; Atractyloside; Glycosides; Hydroquinones; Liver; Necrosis; Plant Poisoning; Plants, Toxic; Swine; Swine Diseases

Callilepis laureola, which has been found to cause fatal liver necrosis in the Black population of Natal, is widely used as a herbal medicine. Chemical extraction has yielded a product, identified as atractyloside, which is responsible for the nephrotoxic and hypoglycaemic effects of Callilepis laureola. The hepatotoxic principle has not yet been isolated.

Topics: Animals; Atractyloside; Chemical and Drug Induced Liver Injury; Kidney Tubular Necrosis, Acute; Methanol; Necrosis; Plant Extracts; Plants, Medicinal; Rats; South Africa