Antioxidant defenses in metal-induced liver damage.
Recent investigations have begun to define more clearly the cellular and molecular roles of oxidant stress in mediating the liver injury and fibrosis of metal storage diseases. Because of a variety of perturbations in antioxidant homeostasis in iron and copper overload, restoring the antioxidant balance to normal, or even exceeding normal levels of selected antioxidants, may provide additional protection against liver injury and prevent the progression to fibrosis and cirrhosis. Inasmuch as GSH levels appear to be elevated in livers of experimentally iron-overloaded animals, attempts to increase this antioxidant should perhaps be limited to copper overload conditions in which hepatic GSH is low. Vitamin C (ascorbate) supplementation should probably be avoided in all metal overload states because of its potentiation of radical generation by transition metals. The safety of beta-carotene in alcoholic liver disease has been questioned. Therefore, until more is known about its toxicity in metal overload, beta-carotene may not be an ideal antioxidant for clinical trials. Vitamin E and related compounds, therefore, appear to be the most reasonable antioxidants to test in metal overload states at this time. In the near future, the results of controlled clinical trials of the use of antioxidants in these and other liver disorders will hopefully provide clearer guidelines for their safety and possible use.
Sokol
R J
RJ
Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado, School of Medicine, Denver, USA.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000627:therapeutic use; D002338:Carotenoids / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury; D003300:Copper / Q000009:adverse effects; D005978:Glutathione / Q000172:deficiency; D007501:Iron / Q000009:adverse effects; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy; D008107:Liver Diseases / Q000188:drug therapy; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy; D008670:Metals / Q000009:adverse effects*; D018384:Oxidative Stress; D014810:Vitamin E / Q000627:therapeutic use; D019207:beta Carotene
D000975:Antioxidants; D008670:Metals; D019207:beta Carotene; D014810:Vitamin E; D002338:Carotenoids; D003300:Copper; D007501:Iron; D005978:Glutathione; D001205:Ascorbic Acid