Paraquat-induced free radical reaction in mouse brain microsomes.
Paraquat has been implicated as an environmental toxin which may induce the syndrome of Parkinson's disease after exposure to this agent. However, the biochemical mechanism by which paraquat causes cell death and neurodegeneration has not been extensively studied. Paraquat was rapidly taken up by nerve terminals isolated from mouse cerebral cortices. It induced lipid peroxidation in a concentration dependent manner in the presence of NADPH and ferrous ion. The maximal stimulation effect was obtained at a paraquat concentration around 100 microM and the Km value for paraquat was 46.7 microM. The lipid peroxidation required microsomal enzymes. Antioxidants, such as superoxide dismutase, catalase and promethazine significantly inhibited paraquat-induced lipid peroxidation. Due to its structural similarity to the pyridinium compound MPP+ (N-methyl-4-phenyl pyridium ion), it may be taken up by dopamine neurons and cause lipid peroxidation and cell death resulting in the manifestation of Parkinsonian syndrome.
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Department of Pharmacology, University of Missouri, Columbia 65212, USA.
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure*; D002374:Catalase / Q000494:pharmacology; D005609:Free Radicals; D007502:Iron Chelating Agents / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008861:Microsomes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D010269:Paraquat / Q000494:pharmacology*; D004369:Pentetic Acid / Q000494:pharmacology; D011398:Promethazine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
D000975:Antioxidants; D005609:Free Radicals; D007502:Iron Chelating Agents; D008315:Malondialdehyde; D009249:NADP; D004369:Pentetic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D011398:Promethazine; D010269:Paraquat