Alcohol and Iron

Iron in its free ferrous and ferric states may serve as a physiological regulator of normal intracellular functions but can be a double-edged sword when linked to several pathways of cellular toxicity. In particular, oxidative stress-induced cytotoxicity leading to both necrosis and apoptosis (so-called necrapoptosis) may be promoted by increased intracellular free iron. When hepatocyte iron accumulates to excess in clinical alcohol abuse or in an experimental, combined model of iron and alcohol hepatotoxicity, there is evidence for synergy among the putative pathways of oxidative stress. Just how excess hepatocyte iron accumulates in alcohol excess is unknown, but when the usual safe harbor for intracellular iron, namely the endosomal-lysosomal compartment, is compromised, it becomes a potent source of free, chelatable pro-oxidant iron. In this regard excess iron in alcohol-induced liver damage and alcohol excess in iron-overload disease are powerful cocktails promoting subcellular organelle damage leading to cell death and fibrogenesis. In some experimental circumstances, only the combined insults of both alcohol and iron overload are capable of inducing cell injury and fibrogenesis. There are clinical examples for such relative resistance to each hepatotoxin presented to the liver in isolation that lend support to this concept of synergy of pro-oxidant pathways of liver injury.

Alcohol and iron - iron overload - hemochromatosis - oxidative stress - lipid peroxidation - fibrogenesis - necrosis - apoptosis

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