S. Abel et Wca. Gelderblom, Oxidative damage and fumonisin B-1-induced toxicity in primary rat hepatocytes and rat liver in vivo, TOXICOLOGY, 131(2-3), 1998, pp. 121-131
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.