Free radicals in tissue damage in liver diseases and therapeutic approach

In vitro and in vivo effects of four hepatoprotective agents: silymarin (LegalonR), (+)-cyanidanol-3 (CatergenR), 6,6-methylene-bis(2,2,4-trimethyl-1, 2-dihydroquinoline) (MTDQ), and 4,5-amino-imidazole-carboxamide-phosphate (Aica-P) on the expression and activity of superoxide dismutase enzyme and on certain cellular immune reactions were studied in lymphocytes (and erythrocytes) from cirrhotic patients and from healthy control subjects. In vitro incubation with these drugs inhibited lectin-induced lymphocyte transformation and some of them decreased the antibody-dependent, spontaneous, and lectin-induced lymphocytotoxicity. MTDQ, silymarin and Aica-P enhanced the superoxide dismutase activity of erythrocytes and lymphocytes and the two latter and (+)-cyanidanol-3 increased the superoxide expression of lymphocytes as measured by flow cytofluorometry. In vivo treatment with Aica-P restored the originally low lymphocyte transformation values of patients' lymphocytes. Our results indirectly suggest that both antioxidant and immunomodulatory activities might be important factors in the hepatoprotective action of these drugs.