Acidosis protects against lethal oxidative injury of liver sinusoidal endothelial cells

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Abstract
The purposes of this study were to determine the pH dependence of lethal endothelial cell injury during oxidative stress and the pH dependence of those cellular mechanisms proposed to result in endothelial cell killing. Oxidative stress was produced in rat liver sinusoidal endothelial cells with H2O2 (5 mmol/L). Cell survival was dependent on the extracellular pH. Indeed, after 180 min of incubation with H2O2, cell survival was only 27% at pH 7.4,45% at pH 6.8 (p 2O2, NAD(P)H oxidation was greater at pH 7.4 than at pH 6.4 (100% vs. 64%, p <0.05). The results indicate that the protective effect of acidosis against cell death during oxidative stress is associated with the inhibition of NAD(P)H oxidation and delayed loss of the mitochondrial membrane potential. Acidosis appears to maintain organelle and cell integrity during oxidative stress by influencing the redox status of NAD(P)H. (HEPATOLOGY 1991;14:150-157.)