Experimental equine aflatoxicosis.

Abstract Adult male Shetland ponies, two per dose level, were given aflatoxin daily at levels of 0.3, 0.15, or 0.075 mg/kg. Signs of toxicosis included inappetence, depression, tremors, and terminal prostration. Deaths occurred at 12 and 16 days (0.3 mg/kg), 25 and 32 days (0.15 mg/kg), and 36 and 39 days (0.075 mg/kg). Prothrombin time, sulfabromophthalein clearance time, total plasma bilirubin, and icteric index increased markedly before death. Elevations in plasma activity of aspartate amino transferase (AST) were observed 1 to 4 days after the start of aflatoxin administration in the high dose group; the AST activity increased significantly and was generally maintained at elevated levels in all groups. There were no elevations in blood urea nitrogen or plasma activity of creatine phosphokinase. At necropsy generalized icterus, hemorrhages, a brown to tan liver, dark reddish brown urine, and dark brown kidneys were consistently observed. Microscopic lesions included centrilobular fatty change, hepatic cell necrosis, and periportal fibrosis in all ponies. These lesions were more prominent in animals given 0.075 mg/kg and were accompanied by a mild bile duct proliferation. Bile stasis, irregularities in size and shape of hepatocytes, and binucleate hepatocytes were also present. A moderate toxic tubular nephrosis was present in some individuals. Ultrastructurally, both vascular endothelium and hepatocytes were severely damaged. There was consistent evidence of bile stasis and destruction of bile canaliculi. The clinical biochemical and pathological findings suggested that the liver was the target organ and that the renal changes were probably secondary.