Regulation of hepatic glutathione metabolism and its role in hepatotoxicity.

The regulation of hepatic glutathione (GSH) metabolism have been reviewed. Key steps in the regulation of hepatic GSH are GSH biosynthesis, the GSH-redox-cycle, the cystathionine pathway, and the carrier-mediated export processes. Possible influences of xenobiotics on these different pathways are discussed. GSH fulfills several essential functions; detoxification of oxygen-derived free radicals, thioldisulfide exchange and storage and transfer of cysteine. GSH is present in all mammalian cells, but may be especially important for organs with intensive exposure to exogenous toxins such as the liver. Within the cell mitochondrial GSH is the main defense against physiological oxidative stress generated by cellular respiration and may be a critical target for toxins. Glutathione homeostasis of the organism is a highly complex process, which is predominantly regulated by the liver but also by skeletal muscle, lung and kidney.