Oxidative stress in the liver and biliary tract diseases

Oxidative stress plays an important role in the pathogenesis of toxic liver diseases and of other hepatic alterations. We summarize the pathomechanism of free radical reactions in liver diseases and the results of experimental and clinical observations. Most of the hepatoprotective drugs belong in the group of free-radical scavengers, their mechanism of action involving membrane stabilization, neutralization of free radicals and immunomodulation. We demonstrate the effects of the different drugs used in the therapy of liver diseases in animal experiments and in human clinicopharmacological studies. The scavenger effect of these drugs has been demonstrated in the subcellular fractions of liver cells in animal experiments. In vitro incubation with some hepatoprotective drugs inhibit lectin-induced lymphocyte transformation while others decrease the antibody-dependent, spontaneous, and lectin-induced lymphocytotoxicity. Dihydroquinolin-type antioxidants and silymarin enhanced the superoxide dismutase activity of erythrocytes and lymphocytes. In addition, in a 6-month double-blind clinical trial of patients with chronic alcoholic liver disease, we studied the effects of silymarin therapy on liver function tests, on the parameters characterizing the oxidative stress and immune reaction, on serum procollagen III peptide level, and on liver histology. A wide range of methods was used. The silymarin preparate corrected the altered immune reaction and the decreased superoxide-dismutase activity of erythrocytes and lymphocytes in patients with alcoholic liver cirrhosis. The results indicate that these drugs exert hepatoprotective activity and can improve liver functions in alcoholic patients and in toxic liver diseases. We found a correlation between the bilirubin concentration and lipid peroxidation in cases with toxic liver and biliary tract diseases, and assume that there are two kinds of bilirubin, an antioxidant and a prooxidant form, on the basis of diene conjugates in the bile.