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 employs the neuronal model, rat pheochromocytoma (PC12) cells to evaluate peroxidation as a toxic mechanism of cyanide. Confocal imaging shows that peroxides form within a few seconds in cell cytoplasm after cyanide exposure and continue to accumulate over a period of several minutes. Peroxide generation by cyanide is decreased to about 50% by phospholipase A2 inhibitors indicating involvement of arachidonic acid in the oxidative process. Also antioxidant defense enzymes (CuZn superoxide dismutase and especially catalase) in PC12 cells are inhibited by cyanide. It appears that peroxide accumulation after cyanide treatment involves both inhibition of breakdown and increased production. Furthermore, both peroxide accumulation and cell death induced by cyanide in PC12 cells are blocked by an antioxidant (ascorbate). These data support the hypothesis that the cytotoxic action of cyanide is related in part to an oxidative process.
Kanthasamy
A G
AG
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907-1334, USA.
Ardelt
B
B
Malave
A
A
Mills
E M
EM
Powley
T L
TL
Borowitz
J L
JL
Isom
G E
GE
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors; D016923:Cell Death / Q000187:drug effects; D003992:Dibucaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D018613:Microscopy, Confocal; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011190:Potassium Cyanide / Q000633:toxicity*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D011796:Quinacrine; D003992:Dibucaine; D011190:Potassium Cyanide; D001205:Ascorbic Acid; D000640:Amitrole