News Release

Free radicals in alcoholic liver disease

Peer-Reviewed Publication

JCI Journals

The fatty degeneration of the liver characteristically seen in alcoholics has been ascribed to cellular damage mediated by free radicals.

Here, Kono et al. identify the macrophage enzyme NADPH oxidase as the source of these troublesome compounds, and they confirm that free radicals are required in the pathogenesis of alcohol-induced liver disease. Covalent adducts, derived in part from the oxidation of ethanol itself, are found in bile from normal mice receiving alcohol on a chronic basis. However, similarly treated mice lacking NADPH oxidase show fewer such adducts, and these animals prove to be completely resistant to liver injury. This same group showed previously that ethanol promotes the release of bacterial endotoxin from the intestine into the circulation, causing liver macrophages (Kupffer cells) to respond with inflammatory modulators. Presumably in response to this bacterial product, activated Kupffer cells in alcohol-fed mice produce the pro-apoptotic protein TNFa, an effect that is blocked in NADPH oxidase-deficient mice but could promote hepatocyte killing in wild type animals. Whether free radicals are also harmful because of direct cytotoxicity, independent of the effects of TNFa, is not resolved here.

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