Experimentally Induced Chronic Aflatoxicosis in Rabbits

Abstract

SUMMARY Male New Zealand White rabbits were given (orally) 4 dosage levels of aflatoxin B 1 ( afb 1 ): 0.025, 0.0375, 0.05, and 0.0625 mg/kg of body weight daily for 24 days. Feed was available ad libitum. Other rabbits were ration-fed without added afb 1 , with the following amounts: 10, 20, 40, 80, and 160 g/day. Clinical condition, feed consumption, selected blood values, and gross and microscopic pathologic changes were determined. The 2 smaller doses of afb 1 did not produce clinical toxicosis or blood changes. The 2 larger doses produced anorexia, decreased weight gains, lethargy, emaciation, dehydration, icterus, and death. Clinicopathologic changes included decreased plasma total protein ( tp ) and increases in blood clotting time, serum bilirubin concentration, and alanine aminotransferase ( alt ) and aspartate aminotransferase ( ast ) activities. There were no consistent dose-related changes in serum alkaline phosphatase ( alp ) activity and little change in pcv and hemoglobin concentration. Reduced feeding did not affect clotting time and serum bilirubin and ast values. Mean values for pcv , hemoglobin, and tp were within usual limits, but gradually decreased with time in animals given 10, 20, and 40 g of feed/day. In the latter rabbits, mean serum alp activity gradually decreased to less than that of control rabbits. Mean serum alt activity was normal except on day 23 when the values were moderately increased in rabbits given 10 and 40 g of feed/day. Gross pathologic changes were observed in most rabbits given 0.05 and 0.0625 mg of afb 1 /kg each day. Icterus of body tissues was apparent, and liver of the icteric animals was yellow to orange. Traces of fresh blood were found within the jejunal lumen. Microscopic changes were observed only in the liver and were more consistent and severe in animals given the daily dosages of 0.05 and 0.0625 mg of afb 1 /kg. Histopathologic changes in liver sections from rabbits given the 0.025 and 0.0375 mg of afb 1 /kg dosage included increased cytoplasmic eosinophilia and loss of cytoplasmic granularity of hepatocytes. In livers of some rabbits, a mild increase in the proportion of binucleate hepatocytes and mild karyomegaly was noted. Bile duct hyperplasia was not evident. Liver sections from rabbits given the 2 larger dose concentrations of afb 1 had similar but more severe changes in hepatocytes. In addition, bile stasis was found within biliary canaliculi of several rabbits. Portal triads in some liver sections contained many cells with fusiform nuclei and little visible cytoplasm. Hepatic necrosis was not detected in any of the rabbits. Hyperplasia of biliary ductular epithelium was seen in 1 rabbit.