Glutathione disulfide formation during naproxen metabolism in the isolated rat hepatocytes

As naproxen was found to induce lipid peroxidation in liver microsomes and isolated hepatocytes of rats during its oxidative metabolism, we studied changes of glutathione on its metabolism. Intracellular oxidized glutathione (GSSG) content increased in isolated rat hepatocytes during naproxen metabolism. The intracellular GSSG increased preceding the production of thiobarbituric acid reactive substances (TBARS) and the release of lactate dehydrogenase (LDH). The glutathione-depleted hepatocytes treated with diethymaleate (DEM) enhanced TBARS production and LDH release, compared to the untreated hepatocytes. The production of GSSG may possibly be an early stage of the naproxen-induced oxidative stress which leads to lipid peroxidation and lethal cell injury.