Inhibition of hypochlorous acid-induced cellular toxicity by nitrite

Chronic inflammation results 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 (HOCI). Exposure of chondrocytic SW1353 cells to HOCI resulted in a concentration- and time-dependent loss in viability, ATP, and glutathione levels. Treatment of cells with NO2- but not nitrate (NO3-) substantially decreased HOCI-dependent cellular toxicity even when NO2- was added at low (muM) concentrations. In contrast, NO2- alone (even at 1 mM concentrations) did not affect cell viability or ATIP and glutathione levels. These data suggest that NO2- accumulation at chronic inflammatory sites, where both HOCI and (NO)-N-. are overproduced, may be cytoprotective against damage caused by HOCI. We propose that this is because HOCI is removed by reacting with NO2- to give nitryl chloride (NO2Cl), which is less damaging in our cell system.