Acute hepatic response to aflatoxin B1 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 carcinogenesis, 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 micrograms/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 micrograms/kg AFB1, these serum parameters remained at control levels. Pathological examination of liver sections indicated no significant lesions at 100 micrograms/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.
Mehta
R
R
Toxicology Research Division, Health and Welfare Canada, Ottawa, Ontario.
Campbell
J S
JS
Laver
G W
GW
Stapley
R
R
Mueller
R
R
D016604:Aflatoxin B1 / Q000008:administration & dosage*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008715:Methionine / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000097:blood
D001786:Blood Glucose; D016604:Aflatoxin B1; D008715:Methionine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002794:Choline; D001663:Bilirubin