MECHANISM OF CYTOTOXICITY OF PARAQUAT .3. THE EFFECTS OF ACUTE PARAQUAT EXPOSURE ON THE ELECTRON-TRANSPORT SYSTEM IN RAT MITOCHONDRIA

The effects of acute paraquat exposure on mitochondrial function in ra t lung were studied. The paraquat dose-response study and time-effecti ve study were performed to prove our hypothesis, enzyme toxicity espec ially in electron transport system following lipid peroxidation of mit ochondrial 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 pa raquat 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 b lood lipid peroxides increased after 6 h of paraquat exposure, decreas ed after 12 and 24 h and increased again after 48 h. After first peak of lipid peroxidation, NQR velocity decreased earlier than NADH:ferric yanide reaction (NFR) velocity. From these results, the cytotoxicity v ia mitochondrial dysfunction by acute paraquat exposure might be cause d by complex I toxicity following lipid peroxidation of mitochondrial inner membrane.