Alteration in Membrane Protein, Antioxidant Status and Hexokinase Activity in Erythrocytes of CCl4- Induced Cirrhotic Rats

Several studies have shown that hepatocyte membrane composition changes in patients with cholestasis and cirrhosis. These alterations that are because of intracellular oxidative stress are supposed to be reflected in erythrocyte membrane. The aim of this study was to investigate the modification of erythrocyte membrane along with hexokinase and antioxidant enzymes during development of cirrhosis. Cirrhosis was induced by intraperitoneal injection of CCl4 in male Wistar rats. The test groups were: baseline, cholestatic, early cirrhotic and advanced cirrhotic along with an equal number of sham-control animals. The erythrocyte membrane modifications (protein sulfhydryl, protein carbonyl, and lipid peroxidation), as well as NO metabolites, were assessed. Activities of GPX, CAT, SOD and HK were also measured. Protein sulfhydryl content of the erythrocyte membrane (after 2, 6 and 10 weeks of injection) had significant progressive decrease. In contrast, protein carbonyls were remarkably increased 2 weeks after injection but significantly decreased after 6 weeks and returned to normal levels after 10 weeks. No significant difference in erythrocyte HK activity or MDA content was observed. Test groups showed significantly lower erythrocyte GPx activity after six weeks and CAT and SOD activities along with NO metabolites content after two weeks (P<0.05). This study indicates that the progression of cirrhosis is accompanied by alterations in antioxidant enzyme and decreased NO metabolites. Protein carbonyl alteration occurs in the early stages of cirrhosis while protein sulfhydryl alterations have a progressive decrease in advanced cirrhosis.