REACTIVE OXYGEN SPECIES GENERATED BY CYANIDE MEDIATE TOXICITY IN RAT PHEOCHROMOCYTOMA CELLS

Peroxide formation has been implicated in impairment of motor function by cyanide which occurs in both animals and man. The present study em ploys the neuronal model, rat pheochromocytoma (PC12) cells to evaluat e peroxidation as a toxic mechanism of cyanide. Confocal imaging shows that peroxides form within a few seconds in cell cytoplasm after cyan ide exposure and continue to accumulate over a period of several minut es. Peroxide generation by cyanide is decreased to about 50% by phosph olipase A(2) inhibitors indicating involvement of arachidonic acid in the oxidative process. Also antioxidant defense enzymes (CuZn superoxi de dismutase and especially catalase) in PC12 cells are inhibited by c yanide. It appears that peroxide accumulation after cyanide treatment involves both inhibition of breakdown and increased production. Furthe rmore, both peroxide accumulation and cell death induced by cyanide in PC12 cells are blocked by an antioxidant (ascorbate). These data supp ort the hypothesis that the cytotoxic action of cyanide is related in part to an oxidative process. (C) 1997 Elsevier Science Ireland Ltd.