Oxidative damage and fumonisin B1-induced toxicity in primary rat hepatocytes and rat liver in vivo.

Dietary fumonisin B1 (FB1) levels of 250 and 500 mg FB1/kg increased the level of thiobarbituric acid reactive substances (TBARS) significantly (P < 0.05) in the liver of rats fed FB1 over 21 days. Levels of 10, 50 and 100 mg FB1/kg also markedly (not significantly) increased the level of TBARS in the liver homogenate. Subcellular fractionation of the liver of the rats fed the 250 mg FB1/kg diet, showed a marginally significant increase of TBARS in the plasma membranes (0.05 < P < 0.1) and a significant increase in the microsomes (P < 0.05). In vitro investigations in primary rat hepatocytes indicated that the level of TBARS was increased in a dose dependent manner associated with an increase in cytotoxicity. Addition of the antioxidant, alpha-tocopherol, significantly decreased the cytotoxicity whereas the level of TBARS was decreased to basal levels, suggesting that lipid peroxidation is likely to contribute to the cytotoxic effect of FB1. Addition of cumene hydroperoxide (CMHP) to primary hepatocytes exposed to FB1 for 44 h, enhanced the CMHP-induced TBARS release suggesting that the hepatocytes exposed to FB1 are more susceptible to chemically-induced oxidative stress. Free radical production could result in excessive cellular damage and/or metabolic abnormalities that are likely to be involved in FB1-induced altered growth responses and cell death in primary hepatocytes. The hepatotoxic effects and resultant oxidative damage induced by FB1 may be important during cancer induction in rat liver by this apparently non-genotoxic compound.