Hydroxyethyl radicals in ethanol hepatotoxicity.
Alcoholic patients and experimental animals exposed to ethanol display biochemical signs of oxidative damage, suggesting a possible role of free radicals in causing some of the toxic effects of alcohol. The use of electron spin resonance (ESR) spectroscopy associated with spin trapping technique has demonstrated that hydroxyethyl radicals are generated during ethanol metabolism by the microsomal monoxygenase system, involving the alcohol-inducible cytochrome P450 2E1 (CYP2E1). Recent observations in rats fed intragastrically with a high fat diet containing ethanol indicate that the formation of hydroxyethyl radicals is associated with stimulation of lipid peroxidation and development of liver damage. Moreover, by alkylating liver proteins, and particularly CYP2E1, hydroxyethyl free radicals are also capable of inducing the production of specific antibodies which can be observed in ethanol-fed animals as well as in patients abusing alcohol. Recent studies have demonstrated that hydroxyethyl radical-derived antigens are exposed on the plasma membranes of hepatocytes exposed to ethanol where are able to target antibody-dependent cell-mediated immunotoxic reactions towards liver cells. Thus, beside to contribute to alcohol-mediated oxidative damage, hydroxyethyl free radicals can contribute by immunological mechanisms to cause hepatocellular lesions associated with alcohol abuse.
Albano
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Department of Medical Sciences, University "A. Avogadro" of East Piedmont, Via Solaroli 17, 28100 Novara, Italy. albano@med.no.unipmn.it
French
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Ingelman-Sundberg
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D000437:Alcoholism / Q000150:complications; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism*; D005609:Free Radicals / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D008107:Liver Diseases / Q000209:etiology; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
D005609:Free Radicals; C065424:1-hydroxyethyl radical; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1