Paraquat is a model environmental neurotoxin for studying Parkinson's disease

Paraquat (PQ) through electron transfer reactions with NADH-dependent oxidoreductase of mitochondria and NADPH-dependent oxidoreductase of microsomal system, generates superoxide, which in the presence of ferrous ion, in turn yields highly reactive free radicals by the Haber-Weiss reaction, thus damages to mitochondrial and other subcellular membranes. Studies from several laboratories have demonstrated that paraquat is able to cross the blood-brain-barrier after systemic injection in rats, implicating PQ as a dopaminergic neurotoxicant in producing syndrome of Parkinsonism and loss of substantia nigra dopaminergic neurons. We have recently reported that paraquat caused lipid peroxidation in a concentration dependent manner, leading to cell death. In the presence of low concentration of chelated iron (Fe2+/DETAPAC), we have demonstrated that paraquat induced the activation of transcription factor, AP-1 and apoptotic cell death in PC12 cells. Cells were also protected from paraquat toxicity in the presence of antioxidant enzymes. The results support the hypothesis that oxidative stress may be the contributing factor to the apoptotic cell death of dopaminergic neurons, leading to the manifestation of Parkinson's disease.