Protection by 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) against the hepatotoxicity of aflatoxin B1 in the rat.
A new chemoprotective agent, oltipraz, was evaluated for alleviation of aflatoxin B1-induced hepatotoxicity. Male F344 rats were fed a diet supplemented with 0.075% oltipraz and compared to rats fed the purified diet (AIN) alone. Rats were fed these diets for 1 week prior to treatment with aflatoxin B1 (AFB1) and throughout the experimental period. AFB1 was administered to rats by gavage in single doses ranging from 0.25 to 10 mg/kg body weight for acute toxicity studies and in multiple doses of 0.25 mg/kg, 5 days/week, for 2 weeks for subchronic toxicity studies. The latter protocol constitutes a tumorigenic dosing regimen. In an acute toxicity study, pretreatment with oltipraz reduced from 83 to 36% the mortality produced by 10 mg/kg AFB1. Oltipraz significantly suppressed the elevated serum levels of alanine amino transaminase and sorbitol dehydrogenase induced by sublethal doses of AFB1. In subchronic toxicity studies, the AFB1-treated rats fed AIN diet failed to gain weight over the 2-week treatment period and their liver weights were severely depressed. In contrast, the rats fed the oltipraz supplemented diet maintained a high rate of growth during AFB1 treatment. The subchronic AFB1 treatment regimen also resulted in over 75% loss of prelabeled [3H]thymidine from the liver while oltipraz supplementation largely prevented this loss. Taken together, these results indicate that oltipraz is very effective in ameliorating the toxic effects of AFB1 in rats.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013871:Thiones; D013876:Thiophenes
D000348:Aflatoxins; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D002084:Butylated Hydroxytoluene; C026209:oltipraz; D004247:DNA; D016604:Aflatoxin B1; D005982:Glutathione Transferase