Effects of paraquat on mitochondria of rat skeletal muscle.
The effect of the herbicide paraquat (N,N'-dimethyl 4,4'-bipyridium), known to damage the lipid cellular membrane by peroxidation with superoxide radicals and a singlet oxygen, was investigated on skeletal muscle mitochondria. Minced rat gastrocnemius muscles were incubated in 8 mM paraquat solution. Mitochondrial fractions prepared from the incubated muscles were examined with respect to respiratory function and the enzyme activity of cytochrome c oxidase and succinate-cytochrome c reductase in the electron transport chain. The ADP/O ratio, RCR, and state 3 rates (= oxygen consumption in state 3) decreased gradually. State 4 rates (= oxygen consumption in state 4) increased in the initial stages and decreased after longer incubations. Enzyme activities gradually increased. These results suggested that paraquat damaged the mitochondrial membrane and disrupted oxidative phosphorylation in the early stage of incubation. Also, the electron transport chain was accelerated in the earlier stage and broken following a longer incubation. The inhibitory modality of paraquat on mitochondrial respiration was shown to be different from that of other known inhibitors.
D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D066298:In Vitro Techniques; D008931:Mitochondria, Muscle / Q000187:drug effects*; D009245:NADH Dehydrogenase / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats
D011773:Pyruvates; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D010269:Paraquat