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    
Abstract/OtherAbstract:
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.
Authors:
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    
Affiliation:
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03756.
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MeSH Terms
Descriptor/Qualifier:
Aflatoxin B1
Aflatoxins / toxicity*
Animals
Body Weight / drug effects
Butylated Hydroxytoluene / pharmacology
DNA / analysis
Enzyme Induction / drug effects
Glutathione Transferase / biosynthesis
Liver / drug effects*,  pathology
Male
Pyrazines / pharmacology*
Rats
Rats, Inbred F344
Grant Support
ID/Acronym/Agency:
CA 23108/CA/NCI NIH HHS; CA 39416/CA/NCI NIH HHS; K04 CA 01230/CA/NCI NIH HHS
Chemical
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 2.5.1.18/Glutathione Transferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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