Document Detail

Protection by 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) against the hepatotoxicity of aflatoxin B1 in the rat.
MedLine Citation:
PMID:  3130679     Owner:  NLM     Status:  MEDLINE    
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.
Y L Liu; B D Roebuck; J D Yager; J D Groopman; T W Kensler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  93     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1988 May 
Date Detail:
Created Date:  1988-06-16     Completed Date:  1988-06-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  442-51     Citation Subset:  IM    
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03756.
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MeSH Terms
Aflatoxin B1
Aflatoxins / toxicity*
Body Weight / drug effects
Butylated Hydroxytoluene / pharmacology
DNA / analysis
Enzyme Induction / drug effects
Glutathione Transferase / biosynthesis
Liver / drug effects*,  pathology
Pyrazines / pharmacology*
Rats, Inbred F344
Grant Support
Reg. No./Substance:
0/Aflatoxins; 0/Pyrazines; 1162-65-8/Aflatoxin B1; 128-37-0/Butylated Hydroxytoluene; 64224-21-1/oltipraz; 9007-49-2/DNA; EC Transferase

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