Estrés Oxidativo

Genes Nutr (2010) 5:101–109
DOI 10.1007/s12263-009-0159-9

REVIEW

Ethanol-induced oxidative stress: basic knowledge
Mario Comporti • Cinzia Signorini • Silvia Leoncini
Concetta Gardi • Lucia Ciccoli • Anna Giardini •
Daniela Vecchio • Beatrice Arezzini

•

Received: 30 July 2009 / Accepted: 9 November 2009 / Published online: 24 December 2009
Ó Springer-Verlag 2009

Abstract Aftera general introduction, the main pathways
of ethanol metabolism (alcohol dehydrogenase, catalase,
coupling of catalase with NADPH oxidase and microsomal
ethanol-oxidizing system) are shortly reviewed. The cytochrome P450 isoform (CYP2E1) specifically involved in
ethanol oxidation is discussed. The acetaldehyde metabolism and the shift of the NAD/NADH ratio in the cellular
environment(reductive stress) are stressed. The toxic
effects of acetaldehyde are mentioned. The ethanolinduced oxidative stress: the increased MDA formation by
incubated liver preparations, the absorption of conjugated
dienes in mitochondrial and microsomal lipids and the
decrease in the most unsaturated fatty acids in liver cell
membranes are discussed. The formation of carbon-centered (1-hydroxyethyl) andoxygen-centered (hydroxyl)
radicals during the metabolism of ethanol is considered: the
generation of hydroxyethyl radicals, which occurs likely
during the process of univalent reduction of dioxygen, is
highlighted and is carried out by ferric cytochrome P450
oxy-complex (P450–Fe3?OÁ-) formed during the reduction
2
of heme-oxygen. The ethanol-induced lipid peroxidation
has been evaluated,and it has been shown that plasma
F2-isoprostanes are increased in ethanol toxicity.
Keywords CYP2E1 isoform Á Ethanol metabolism Á
Hydroxyethyl radicals Á Liver-free non-protein bound iron Á
Oxidative stress Á Plasma isoprostanes

M. Comporti (&) Á C. Signorini Á S. Leoncini Á C. Gardi Á
L. Ciccoli Á A. Giardini Á D. Vecchio Á B. Arezzini
Department of Pathophysiology,
ExperimentalMedicine and Public Health,
University of Siena, via A. Moro, 53100 Siena, Italy
e-mail: comporti@unisi.it

Introduction
Ethanol unlike many other hepatotoxic chemicals is not a
foreign substance for living organisms; it occurs, in fact, in
small amounts in mammalian tissues [82] and is conceivably formed by the alcohol dehydrogenase-catalyzed
reduction of acetaldehyde derived from thedecarboxylation of the intermediary metabolite pyruvate [83]. A similar reaction also occurs in biological fermentation (such as
that yielding ethyl alcohol in wine and other alcoholic
beverages) in which glucose is fermented by yeast. Moreover, significant amounts of ethanol are normally formed in
the gastrointestinal tract, absorbed by the portal vein and
metabolized in the liver [64]; most alcohol isof microbial
origin, the other portion probably arising from the acetaldehyde formed by the normal pathways of degradation of
threonine, deoxyribose phosphate and b-alanine. Furthermore, ethanol is rapidly and most entirely converted to the
key intermediate, acetate, which can enter a wide-spread
variety of metabolic pathways. This ‘‘more physiological’’
aspect of ethanol when compared withother hepatotoxic
drugs complicates to a large extent the study of the
mechanisms involved in the pathogenetic effects of alcohol. The great interest on ethylism from both a clinical and
a sociological point of views resulted in an impressive
number of studies on the effects of ethyl alcohol. However,
the results have not been even univocal because the models
used (alcohol dosage, acute orchronic administration,
animals studied, different susceptibility to ethanol consumption, sex, nutritional status, etc.) have been extremely
variable. Even the choice of the model itself for the study is
questionable: in fact, if the acute (single large dose of
alcohol) intoxication is a model more suitable for the study
of the direct effects of ethanol at the cellular, subcellular
and...