Inhibition of hypochlorous acid-induced cellular toxicity by nitrite

Abstract

Chronic inflammation results in increased nitrogen monoxide (·NO) formation and the accumulation of nitrite (NO2-). 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 NO2- but not nitrate (NO3-) substantially decreased HOCl-dependent cellular toxicity even when NO2- was added at low (μM) concentrations. In contrast, NO2- alone (even at 1 mM concentrations) did not affect cell viability or ATP and glutathione levels. These data suggest that NO2- 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 NO2- to give nitryl chloride (NO2Cl), which is less damaging in our cell system.