Oxidative stress in isolated rat hepatocytes during naproxen metabolism.

Naproxen, a non-steroidal anti-inflammatory drug, induced lipid peroxidation in isolated hepatocytes of rats. The viability of the hepatocytes decreased upon lipid peroxidation, and this effect was accompanied by the formation of high molecular weight protein aggregates in the hepatocytes. Protein aggregation occurred slowly compared with the formation of thiobarbituric acid reactive substances (TBARS). The increase of TBARS was strongly correlated with the decrease of intracellular glutathione. Chemiluminescence was produced from the hepatocyte suspension during naproxen metabolism, and was correlated with the formation of TBARS. These results indicate that lipid peroxidation in the hepatocytes was provoked by reactive oxygens produced in the process of naproxen metabolism.