ACUTE HEPATIC RESPONSE TO AFLATOXIN-B(1) IN RATS FED A METHYL-DEFICIENT, AMINO ACID-DEFINED DIET

In order to evaluate the relative contribution of aflatoxin B1 (AFB1)-induced toxicity towards a methyl-deficient diet influenced AFB1 arcinogenesis, a no-observed-effect-level (NOEL) for AFB1, with reference to liver damage, was determined in rats fed a nutritionally complete amino acid-defined basal (CMS) diet or a choline-methionine-deficient (CMD) diet. After 3 weeks of dietary treatment, male Fischer 344 rats received a single, oral dose of AFB1 in the range of 100-600 pg/kg body weight. At 24, 48 and 72 h after AFB1 treatment, six serum biochemical parameters were analysed in parallel with histological examination of liver sections. In rats fed the CMS diet and receiving 250-600 mug/kg AFB1, serum levels of glutamyl oxalo-transaminase (SGOT), glutamyl pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin increased, glucose levels decreased and gamma glutamyl transpeptidase (GGT) levels remained unchanged over the 72-h period following mycotoxin treatment. However, at 100 mug/kg AFB1, these serum parameters remained at control levels. Pathological examination of liver sections indicated no significant lesions at 100 mug/kg AFB1 confirming this as the non-necrogenic dose or NOEL in CMS diet group rats. In contrast, in CMD diet fed rats, serum or pathology data showed no obvious time- or dose-response to mycotoxin treatment, extensive hepatic lipidosis in response to dietary treatment being the only predominant lesion in this diet group. The milder response of CMD rat livers to a single dose of AFB1 suggest a possible reduction in the susceptibility of these livers to AFB1 toxicity.