Inhibition of hypochlorous acid-induced cellular toxicity by nitrite

摘要

Chronic inflammation results in increased nitrogen monoxide (·NO) formation and the accumulation of nitrite (NO_2~-). Neutrophils stimulated by various inflammatory mediators release myeloper-oxidase 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 NO_2~- but not nitrate (NO_3~-) substantially decreased HOCl-dependent cellular toxicity even when NO_2~- was added at low (μM) concentrations. In contrast, NO_2~- alone (even at 1 mM concentrations) did not affect cell viability or ATP and glutathione levels. These data suggest that NO_2~- accumulation at chronic inflammatory sites, where both HOCI and ·NO are overproduced, may be cytoprotective against damage caused by HOCI. We propose that this is because HOCI is removed by reacting with NOJ to give nitryl chloride (NO_2Cl), which is less damaging in our cell system.