Ethanol-induced oxidative stress: basic knowledge.
After a 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 P(450) 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 ethanol-induced 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) and oxygen-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 P(450) oxy-complex (P(450)-Fe(3+)O(2) (.-)) formed during the reduction of heme-oxygen. The ethanol-induced lipid peroxidation has been evaluated, and it has been shown that plasma F(2)-isoprostanes are increased in ethanol toxicity.
Comporti
Mario
M
Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, via A. Moro, 53100 Siena, Italy.
Signorini
Cinzia
C
Leoncini
Silvia
S
Gardi
Concetta
C
Ciccoli
Lucia
L
Giardini
Anna
A
Vecchio
Daniela
D
Arezzini
Beatrice
B