APPARENT ROLE OF HYDROXYL RADICALS IN OXIDATIVE BRAIN INJURY-INDUCED BY SODIUM-NITROPRUSSIDE

Sodium nitroprusside (disodium nitroferricyanide) has been suggested t o cause cytotoxicity through either the release of cyanide and/or nitr ic oxide. The present study investigated a possible mechanism that aft er a brief release of nitric oxide, iron moiety of breakdown products of sodium nitroprusside could cause a lone lasting oxidative stress, s uch as hydroxyl radical generation, lipid peroxidation and cytotoxicit y. Intranigral administration of sodium nitroprusside (0-16.8 nmol) to rats induced an acute increase in lipid peroxidation in the substanti a nigra and a chronic dopamine depletion in the caudate nucleus. Photo degraded (nitric oxide-exhibited) sodium nitroprusside, however, still produced lipid peroxidation and neurotoxicity in the midbrain. Moreov er, non-iron containing nitric oxide-donor compounds, such as S-nitros o-N-acetylpenicillamine, did not cause oxidative brain injury in vivo suggesting that nitric oxide may not mediate neurotoxicity induced by sodium nitroprusside. Additional in vitro studies demonstrated that bo th freshly prepared (nitric oxide donor) and photodegraded (nitric oxi de-exhausted) sodium nitroprusside generated hydroxyl radicals in the presence of ascorbate and also increased lipid peroxidation in brain h omogenates. These pro-oxidative effects of sodium nitroprusside were b locked by nitric oxide, S-nitroso-N-acetylpenicillamine, oxyhemoglobin , and deferoxamine (iron chelator). The present results suggest that i ron moiety, rather than nitric oxide, may mediate the pro-oxidative pr operties of sodium nitroprusside. With this new information in mind, t he misuse of sodium nitroprusside as a selective nitric oxide donor in both basic and clinical uses should be urgently addressed. Published by Elsevier Science, Inc.