Effect of ethanol on hepatotoxicity and hepatic DNA-binding of aflatoxin B1 in rats

Biochemical Pharmacology
C J WangJ K Lin

Abstract

The hepatocarcinogen aflatoxin B1 is converted to reactive metabolites that bind covalently to cellular macromolecules. These metabolites may also react with glutathione, resulting in the formation of glutathione conjugates and detoxication of the reactive metabolite. When rats were pretreated with ethanol by gastric intubation at a dose of 100 mmol/kg, 6 hr (the time of maximal GSH depletion) before the administration of aflatoxin B1, the covalent binding of 8,9-epoxide-aflatoxin B1 to DNA in vivo was increased by 47% and the hepatotoxicity was also potentiated. However, the covalent binding was not increased by pretreatment with ethanol 18 hr (time with approximately normal GSH levels) before administration of the toxin, and no potentiation of hepatotoxicity was observed. Pretreatment with a non-toxic dose of ethanol had no effects on the activity of glutathione S-transferase and glutathione peroxidase. These results suggest that the depletion of GSH and the increased formation of DNA-adduct from the liver constitute an important mechanism for the potentiation of aflatoxin B1-induced hepatotoxicity by ethanol.

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Citations

Apr 1, 1994·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·C Y ChuC J Wang
Jan 1, 1992·Free Radical Biology & Medicine·R NordmannH Rouach
Jan 4, 1998·Journal of Gastroenterology and Hepatology·H IshiiS Kato
Feb 1, 1996·Alcoholism, Clinical and Experimental Research·I KuroseH Ishii
Mar 9, 2007·Biochemical Pharmacology·Barbara L Vogt, John P Richie
Oct 27, 2004·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·W Łuczaj, E Skrzydlewska
Aug 22, 2009·Toxicology Mechanisms and Methods·Wojciech LuczajBogusław Buszewski

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