AFLATOXIN B-1-INDUCED LIPID-PEROXIDATION IN RAT-LIVER

Aflatoxin B-1 (AFB(1)) is a potent hepatotoxic and hepatocarcinogenic mycotoxin. The mechanism of cellular damages caused by AFB(1) has not been fully elucidated. Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenesis of many carcinogens. In this study, we investigated the induction of lipid peroxidation by AFB(1) in the liver of Fischer 344 rats. Malonaldehyde (MDA) and conjugated dienes, both products of lipid peroxidation, were determined in liver homogenate and subcellular fractions. An increase of MDA and conjugated dienes in liver homogenate was detected 1 day after AFB(1) administration. It reached the peak level 3 days after dosing and remained at an elevated level up to 14 days. The induction of MDA by AFB(1) was also found to be dose-dependent. Measurements of lipid peroxidation in the subcellular fractions revealed that microsomes had the highest concentration of MDA, followed by those of the nuclear fraction and mitochondria. MDA concentration was not detectable in the cytosolic fraction. Further, it was found that pretreatment with selenium and vitamin E, both antioxidants, and deferoxamine, a specific iron chelator, significantly inhibited lipid peroxidation as well as liver cell damage. These results provide in vivo evidence that AFB(1) can cause lipid peroxidation in rat liver. Oxidative damages caused by AFB(1) may be one of the underlining mechanisms for AFB(1)-induced cell injury and DNA damage, which eventually lead to tumorigenesis. (C) 1994 Academic Press, Inc.