Possible Interaction: Ethanol and Iron, Dietary

“ Ethanol consumption and/or liver damage may alter liver content of several trace elements, as iron , zinc, copper, and manganese.”

“For example, plasminogen activator inhibitor 1 was shown to play a central role for steatosis, the anti-inflammatory adipokine, adiponectin profoundly regulates liver macrophage function and excessive hepatic deposition of iron is caused by chronic ethanol intoxication and increases the risk of hepatocellular carcinoma development.”

“In addition to its independent role as a proxidant, high levels of free iron may potentiate the effects of estradiol, ethanol , and ionizing radiation—three established risk factors for breast cancer.”

“Consequently, there is persuasive evidence that the potential of ethanol and iron to induce oxidative stress may be an important pathogenic mechanism for the increased occurrence of hepatocellular carcinoma in individuals with hepatic iron overload who ingest alcohol.”

“In addition, the accumulation of iron in hepatic macrophage isolated from laboratory animals chronically ingesting alcohol is associated with activation of nuclear factor-kappa B and production of tumor necrosis factor-alpha, providing a proinflammatory cellular environment also favorable for initiation and promotion of carcinogenesis.”

“One cellular consequence of sustained oxidative stress and redox imbalance resulting from the combined actions of alcohol and iron is lipid peroxidation, resulting in the production of aldehydic products such as 4-hydroxy-2-nonenal, which has been linked to site-specific mutations of the p53 gene.”

“The combined prooxidant potential of ethanol and iron is at least additive and possibly synergistic with respect to inducing hepatocellular oxidative stress and antioxidant depletion.”

“In addition, iron may enhance the cytotoxic and, possibly, fibrogenic effects of other liver cell-damaging agents, such as alcohol or hepatotrophic viruses.”

“Evidence is presented that in utero exposure to alcohol , iron-deficient diets, and dysfunctional oligodendrocytes can influence the normal pattern for iron accumulation in the brain which sets off a cascade of events that results in loss of regulatory control of iron.”

“Though alcoholism alone could explain her presentation, we hypothesize that an inflammatory cocktail of iron and alcohol probably caused our patient to succumb to acute liver failure at a very young age.”

“Our findings therefore suggest that iron could CPY2E1-independently enhance the oxidative stress induced by alcohol , which probably contributes to the pathogenesis of alcoholic liver disease.”

“Specifically, the interactions between alcohol and secondary risk factors (high-fat diet, iron , tobacco, medications, female gender) and comorbidities (viral hepatitis, diabetes) are of urgent epidemiological importance.”

“Understanding these molecular mechanisms is of considerable clinical importance because both alcoholic liver disease and genetic hemochromatosis are common diseases, in which alcohol and iron appear to act synergistically to cause liver injury.”