Hepatic lipid peroxidation and intracellular calcium accumulation in ethanol potentiated aflatoxin B1 toxicity.
The possible role of hepatic lipid peroxidation and Ca2+ in enhanced hepatotoxicity of aflatoxin B1 (AFB1) by ethanol was examined along with changes in hepatic glutathione in male rats. Hepatic glutathione (GSH) was markedly decreased (43.9%) at 12 h after AFB1 administration in rats treated with ethanol (4.0 g/kg BW) and AFB1 (2.0 mg/kg BW) when compared to AFB1 alone. At 24 h after AFB1 administration, hepatic lipid peroxide levels in subcellular fractions, particularly in microsomes, were significantly increased (76.9%) in rats treated with ethanol and AFB1 following the decrease in hepatic GSH content. Hepatic lipid peroxide levels returned to normal values at about 48 h after AFB1 administration. Furthermore, Ca2+ in whole liver (60.9%), microsomes (83.8%) and mitochondria (51.2%) were significantly increased in the rats treated with ethanol and AFB1 as compared to those rats treated with AFB1 alone at 48 h after toxin administration. The increase in hepatic Ca2+ in rats treated with ethanol and AFB1 was a possible consequence of the increase in hepatic lipid peroxide. These findings suggest that there is a close relationship between hepatic GSH content, lipid peroxidation and intracellular accumulation of Ca2+. The pronounced effects on hepatic lipid peroxidation and intracellular accumulation of Ca2+ could play a role in ethanol-induced potentiation of AFB1 hepatotoxicity in rats.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000348:Aflatoxins; D008054:Lipid Peroxides; D000431:Ethanol; D016604:Aflatoxin B1; D002118:Calcium