Oxidative damage and fumonisin B-1-induced toxicity in primary rat hepatocytes and rat liver in vivo

Dietary fumonisin B-1 (FB1) levels of 250 and 500 mg FB1/kg increased the l evel 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 m g FB1/kg also markedly (not significantly) increased the level of TEARS in the liver homogenate. Subcellular fractionation of the liver of the rats fe d the 250 mg FB1/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 in dicated that the level of TEARS was increased in a dose dependent manner as sociated with an increase in cytotoxicity. Addition of the antioxidant, a-t ocopherol, significantly decreased the cytotoxicity whereas the level of TE ARS was decreased to basal levels, suggesting that lipid peroxidation is li kely to contribute to the cytotoxic effect of FB1. Addition of cumene hydro peroxide (CMHP) to primary hepatocytes exposed to FB1 for 44 h, enhanced th e CMHP-induced TEARS 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 abnor malities that are likely to be involved in FB1-induced altered growth respo nses and cell death in primary hepatocytes. The hepatotoxic effects and res ultant oxidative damage induced by FB, may be important during cancer induc tion in rat liver by this apparently non-genotoxic compound. (C) 1998 Elsev ier Science Ireland Ltd. All rights reserved.