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 experimenta l and clinical observations. Most of the hepatoprotective drugs belong in t he group of free-radical scavengers, their mechanism of action involving me mbrane stabilization, neutralization of free radicals and immunomodulation. We demonstrate the effects of the different drugs used in the therapy of l iver diseases in animal experiments and in human clinicopharmncological stu dies. The scavenger effect of these drugs has been demonstrated in the subc ellular fractions of liver cells in animal experiments. In vitro incubation with some hepatoprotective drugs inhibit lectin-induced lymphocyte transfo rmation while others decrease the antibody-dependent, spontaneous, and lect in-induced lymphocytotoxicity. Dihydroquinolin-type antioxidants and silyma rin enhanced the superoxide dismutase activity of erythrocytes and lymphocy tes, In addition, in a 6-month double-blind clinical trial of patients with chronic alcoholic liver disease, we studied the effects of silymarin thera py 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-dismutas e activity of erythrocytes and lymphocytes in patients with alcoholic liver cirrhosis. The results indicate that these drugs exert hepatoprotective ac tivity and can improve liver functions in alcoholic patients and in toxic l iver diseases. We found a correlation between the bilirubin concentration a nd lipid peroxidation in cases with toxic liver and biliary tract diseases, and assume that there are two kinds of bilirubin, an antioxidant and a pro oxidant form, on the basis of diene conjugates in the bile.