Alcohol and the liver: 1994 update

Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress

“…Decreased mitochondrial function results in inhibition of fatty acid oxidation and ATP formation. Both factors favor the occurrence of fatty liver (Lieber, 1994). In addition, mitochondrial damage induces apoptosis, but also survival factors such as NF-kB.…”

“…(1) Chronic alcohol interacts with intake, absorption and subsequent metabolism of B vitamins involved in hepatic transmethylation reactions, namely folate and pyridoxal-59-phosphate (vitamin B 6 ), resulting in impaired methyl group synthesis and transfer (Lumeng and Li, 1974;Labadarios et al, 1977;Savage and Lindenbaum, 1986;Gloria et al, 1997;Stickel et al, 2000). (2) Ethanol reduces the activity of methionine synthetase, which remethylates homocysteine to methionine with methyltetrahydrofolate as the methyl donor (Barak et al, 1993;Lieber, 1994). (3) Chronic alcohol consumption decreases glutathione levels, a reductive tripeptide that is synthesized from homocysteine via trans-sulfuration in the liver, and thereby enhances the susceptibility of the liver to alcohol-related peroxidative damage (Speisky et al, 1985;Lieber, 1994).…”

“…(2) Ethanol reduces the activity of methionine synthetase, which remethylates homocysteine to methionine with methyltetrahydrofolate as the methyl donor (Barak et al, 1993;Lieber, 1994). (3) Chronic alcohol consumption decreases glutathione levels, a reductive tripeptide that is synthesized from homocysteine via trans-sulfuration in the liver, and thereby enhances the susceptibility of the liver to alcohol-related peroxidative damage (Speisky et al, 1985;Lieber, 1994). (4) Alcohol can inhibit the activity of DNA methyltransferase, which transfers methyl groups to DNA in rats (Lieber et al, 1990), a finding that could not, however, be confirmed in humans (Miyakawa et al, 1996).…”

Recommendations for the nutritional management of patients with diabetes mellitus

“…Alcohol effects of special note include danger of hypoglycaemia in fasting individuals primarily due to suppression of gluconeogenesis (Lieber, 1994). Sulphonylurea usage compounds the danger in those with NIDDM.…”

Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat

“…1 Several lines of investigation indicate that endotoxin and oxidative stress are important pathogenic mechanisms in alcohol-induced liver injury. [1][2][3][4][5] It is well known that endotoxin is hepatotoxic and concentrations of endotoxin increase in experimental and human alcoholic liver disease. 2,3,6,7 Lipid peroxides are also potentially hepatotoxic and increased levels are seen after alcohol administration.…”