Inhibition of hypochlorous acid-induced cellular toxicity by nitrite

Chronic inflammation results in increased nitrogen monoxide (⋅NO) formation and the accumulation of nitrite (NO [Formula: see text]). Neutrophils stimulated by various inflammatory mediators release myeloperoxidase to produce the cytotoxic agent hypochlorous acid (HOCl). Exposure of chondrocytic SW1353 cells to HOCl resulted in a concentration- and time-dependent loss in viability, ATP, and glutathione levels. Treatment of cells with NO [Formula: see text] but not nitrate (NO [Formula: see text]) substantially decreased HOCl-dependent cellular toxicity even when NO [Formula: see text] was added at low (μM) concentrations. In contrast, NO [Formula: see text] alone (even at 1 mM concentrations) did not affect cell viability or ATP and glutathione levels. These data suggest that NO [Formula: see text] accumulation at chronic inflammatory sites, where both HOCl and ⋅NO are overproduced, may be cytoprotective against damage caused by HOCl. We propose that this is because HOCl is removed by reacting with NO [Formula: see text] to give nitryl chloride (NO(2)Cl), which is less damaging in our cell system.