Mechanism of cytotoxicity of paraquat. III. The effects of acute paraquat exposure on the electron transport system in rat mitochondria.

The effects of acute paraquat exposure on mitochondrial function in rat lung were studied. The paraquat dose-response study and time-effective study were performed to prove our hypothesis, enzyme toxicity especially in electron transport system following lipid peroxidation of mitochondrial inner membrane. In dose-response study, lipid peroxidation was increased by high dose paraquat exposure (40 mg/kg body weight) in rat lung, but not by low dose exposure (10 mg/kg body weight). But paraquat inhibited NADH:ubiquinone oxidoreductase (complex I) activities, especially NADH:ubiquinone reaction (NQR), even in low dose exposure. The lipid peroxide concentration did not correspond to the damage of complex I activity. In paraquat time-effective study, both lung and blood lipid peroxides increased after 6 h of paraquat exposure, decreased after 12 and 24 h and increased again after 48 h. After first peak of lipid peroxidation, NQR velocity decreased earlier than NADH:ferricyanide reaction (NFR) velocity. From these results, the cytotoxicity via mitochondrial dysfunction by acute paraquat exposure might be caused by complex I toxicity following lipid peroxidation of mitochondrial inner membrane.