Acute and chronic inflammation result in increased nitrogen monoxide ((NO)-N-.) formation and the accumulation of nitrite (NO2-). Neutrophils stimulated by various inflammatory mediators release myeloperoxidase to produce the cytotoxic agent hypochlorous acid (HOCl). At physiologically attainable concentrations, we found that NO2- significantly inhibits HOCl-mediated DNA strand breakage and ascorbate depletion. HOCl-mediated inactivation of pure alpha(1)-antiproteinase or of the elastase inhibitory capacity of human plasma was inhibited by the addition of NO2-. NO2- was more effective than ascorbate, GSH, and urate at inhibiting HOCl-mediated toxicity to human HepG2 cells in culture. These data suggest that NO2- may act in an antioxidant manner by removing HOCl at sites of inflammation where both HOCl and (NO)-N-. are overproduced. (C) 2003 Elsevier Science (USA). All rights reserved.