NITRIC-OXIDE (NO) PROTECTS AGAINST CELLULAR-DAMAGE BY REACTIVE OXYGENSPECIES

Since the discovery of nitric oxide (NO) as an endogenously formed rad ical, its effect on numerous physiological processes has been intensiv ely investigated. Some studies have suggested NO to be cytotoxic while others have demonstrated it protective under various biological condi tions. Though NO shows minimal cytotoxicity to a variety mammalian cel l cultures, it does modulate the toxicity of some agents such as react ive oxygen species. Often, NO is generated in the presence of these re active oxygen species in response to foreign pathogens or under variou s pathophysiological conditions. We will show that NO can play a prote ctive role under oxidative stress resulting from superoxide, hydrogen peroxide and alkyl peroxides. It was found by measuring the time-conce ntration profiles of NO released from various NO donor compounds that only mu M levels of NO were required for protection against the toxici ty of these reactive species. It was found that there are several chem ical reactions which may account for these protective effects such as NO preventing heme oxidation, inhibition of Fenton-type oxidation of D NA, and abatement of lipid peroxidation. Taken together, NO at low con centrations clearly protects against peroxide-mediated toxicity.