title: Mechanism of cytotoxicity of paraquat. III. The effects of acute paraquat exposure on the electron transport system in rat mitochondria.
abstract: 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.
authors.affiliation: Department of Environmental Medicine, Shimane Medical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukushima
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: N
authors.initials: N
authors.lastname: Hojo
authors.forename: A
authors.initials: A
authors.lastname: Isobe
authors.forename: K
authors.initials: K
authors.lastname: Shiwaku
authors.forename: Y
authors.initials: Y
authors.lastname: Yamane
mesh_terms: D000818:Animals; D004579:Electron Transport / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010269:Paraquat / Q000097:blood / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010269:Paraquat