beta-carotene and Liver-Diseases--Alcoholic

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.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Chemical and Drug Induced Liver Injury; Copper; Glutathione; Iron; Liver Cirrhosis, Experimental; Liver Diseases; Liver Diseases, Alcoholic; Metals; Oxidative Stress; Vitamin E

Alcoholics admitted for detoxification were entered into a double blind placebo controlled trial of oral supplementation with an antioxidant cocktail (vitamin E, beta carotene, vitamin C and selenium) in order to determine the effect of this supplementation on the rate of resolution of a serum marker of free radical activity and abnormal serum biochemistry. The molar proportion of linoleic acid that was diene conjugated (a marker of free radical activity), was increased in the alcoholics 2.9% +/- 1.2 (mean +/- S.D.) compared to normal controls 1.3% +/- 0.6 (P < 0.0001) but fell at a similar rate during the first week of hospitalisation in supplemented and placebo-treated patients with a mean fall of 53.7% (+/- 16.4 S.D.) in the placebo group and 56.0% (+/- 23.7) (P = 0.32, NS) in the antioxidant supplemented group. Similarly, there was no difference in the rate of fall between serum aspartate transaminase (AST) concentration in the two groups: the placebo group falling by a mean of 68.9% (+/- 35.2) and the antioxidant supplemented group falling by 70.1% (+/- 10.0) (P = 0.41, NS) over the first 7 days of hospitalization. Alcoholics had low serum concentrations of vitamin E compared with controls (15.6 mg/l +/- 6.2 S.D.) which rose more in the supplemented group over the period of a week (7.7 mg/l +/- 4.4 to 21.6 mg/l +/- 5.1) (a mean rise of 180.5%) compared with the placebo group (8.6 mg/l +/- 6.8 to 9.6 mg/l +/- 5.7)--a mean rise of 11.6% (P = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Carotenoids; Double-Blind Method; Drug Therapy, Combination; Ethanol; Female; Free Radicals; Hematologic Tests; Humans; Liver Diseases, Alcoholic; Male; Middle Aged; Selenium; Substance Withdrawal Syndrome; Vitamin E

The antioxidant status of alcoholic patients was assessed by direct measurement of the plasma antioxidants alpha-tocopherol and beta-carotene and of selenium as a marker of glutathione peroxidase. Overall, the alcoholic group showed significant decreases in the mean plasma values of beta-carotene, zinc and selenium when compared to the control subjects. When the patients were subdivided according to their liver histology, beta-carotene showed a progressive decrease in plasma concentration with increasing liver damage, whereas alpha-tocopherol levels were only depleted in the patients with cirrhosis. There were significant decreases in the plasma concentrations of both alpha-tocopherol and selenium in all patients with alcoholic skeletal muscle myopathy, whereas patients with normal muscle biopsies showed adequate antioxidant status. Such results support a role for free radical-mediated damage in end organ injury, particularly myopathy, in alcohol misusers.

Topics: Adult; Alcoholism; Antioxidants; beta Carotene; Biopsy; Carotenoids; Fatty Liver, Alcoholic; Female; Humans; Liver; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Liver Function Tests; Male; Middle Aged; Muscles; Muscular Diseases; Selenium; Vitamin A; Vitamin E