Glutathione S-transferase in alcoholic fatty liver

Hepatic glutathione (GSH) S-transferase (GST) activity and the tissue distribution of a cationic GST were investigated in biopsy liver samples obtained from patients with alcoholic liver diseases. GST activities in alcoholic fatty liver were significantly high, whereas those in cirrhosis were significantly low compared with normal liver. In fatty liver, immunohistochemically, the staining of the enzyme was strongly positive in hepatocytes around intensive fatty metamorphosis. Then, using experimental chronic alcohol-fed rats, the changes in hepatic GST and GSH peroxidase (GPx) activities and lipid peroxide (LPO) and GSH contents in alcoholic fatty liver were evaluated. Hepatic GST isoenzymes were analyzed and tissue distribution of cationic and neutral GSTs was also investigated. Liver GSH content decreased at two weeks and increased at six weeks. Liver LPO content was elevated at four and six weeks and cytosolic GPx activity was enhanced at four weeks. Cytosolic GST activity was enhanced at six weeks. The cationic and neutral GST isoenzyme pattern was unchanged compared with normal liver. Immunohistochemically, the distribution and intensity of the staining of GSTs were essentially unchanged. There was no evidence of an increase in the GST isoenzyme with selen-independent GPx activity. However, GSTs were strongly stained in the hepatocytes with fatty droplets. Thus, in alcoholic fatty liver, hepatic GST and GPx activities are thought to be enhanced by different mechanisms. The elevated GPx activity may relate to the production of LPO. However, the enhancement of GST activity may result from some other causes which include the enzyme induction.