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

Dietary fumonisin B(1) (FB(1)) levels of 250 and 500 mg FB(1)/kg increased the level of thiobarbituric acid reactive substances (TBARS) significantly (P < 0.05) in the liver of rats fed FB(1) over 21 days. Levels of 10, 50 and 100 mg FB(1)/kg also markedly (not significantly) increased the level of TEARS in the liver homogenate. Subcellular fractionation of the liver of the rats fed the 250 mg FB(1)/kg diet, showed a marginally significant increase of TEARS 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 TEARS was increased in a dose dependent manner associated with an increase in cytotoxicity. Addition of the antioxidant, a-tocopherol, significantly decreased the cytotoxicity whereas the level of TEARS was decreased to basal levels, suggesting that lipid peroxidation is likely to contribute to the cytotoxic effect of FB(1). Addition of cumene hydroperoxide (CMHP) to primary hepatocytes exposed to FB(1) for 44 h, enhanced the CMHP-induced TEARS release suggesting that the hepatocytes exposed to FB(1) 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 FB(1)-induced altered growth responses and cell death in primary hepatocytes. The hepatotoxic effects and resultant oxidative damage induced by FB, may be important during cancer induction in rat liver by this apparently non-genotoxic compound. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.