PARAQUAT-INDUCED CELL-DEATH IN PC12 CELLS

Paraquat was taken up by PC12 cells in a carrier-mediated, saturable m anner. When PC12 cells were permeabilized with digitonin (50 mu g/ml) lipid peroxidation was observed after paraquat treatment in the presen ce of NADPH and chelated iron. The fact that lipid peroxidation preced ed the appearance of LDH release provides positive evidence that lipid peroxidation may be one of the important factors leading to cytotoxic ity of cells. Furthermore, the fact that addition of superoxide dismut ase, catalase and promethazine efficiently blocked the malondialdehyde formation and attenuated the cell death indicated the involvement of reactive oxygen radicals in mediating the cytotoxicity induced by para quat. Taken together the results present in vitro evidence that neurot oxicity of paraquat may be a consequence of cellular lipid peroxidatio n, which leads to cell death and may have great implications in assess ing the risk of exposure to paraquat in Parkinson's disease.