PARAQUAT-INDUCED FREE-RADICAL REACTION IN MOUSE-BRAIN MICROSOMES

Paraquat has been implicated as an environmental toxin which may induc e the syndrome of Parkinson's disease after exposure to this agent. Ho wever, the biochemical mechanism by which paraquat causes cell death a nd neurodegeneration has not been extensively studied. Paraquat was ra pidly taken up by nerve terminals isolated from mouse cerebral cortice s. It induced lipid peroxidation in a concentration dependent manner i n the presence of NADPH and ferrous ion. The maximal stimulation effec t was obtained at a paraquat concentration around 100 mu M and the K-m value for paraquat was 46.7 mu M. The lipid peroxidation required mic rosomal enzymes. Antioxidants, such as superoxide dismutase, catalase and promethazine significantly inhibited paraquat-induced lipid peroxi dation. Due to its structural similarity to the pyridinium compound MP P+ (N-methyl-4-phenyl pyridium ion), it may be taken up by dopamine ne urons and cause lipid peroxidation and cell death resulting in the man ifestation of Parkinsonian syndrome.