Deleterious effects induced by oxidative stress in liver nuclei from rats receiving an alcohol containing liquid diet

M. I. DÍAZ GÓMEZ,; S.L. FANELLI ; A.M.A. DELGADO DE LAYÑO,; F.M. BIETTO,; J.A. CASTRO; G.D. CASTRO

TOXICOLOGY AND INDUSTRIAL HEALTH

SAGE Publications

Lugar: Londres; Año: 2008 vol. 24 p. 625 - 634

0748-2337

Highly purified rat-liver nuclei were previously shown to have nuclear ethanol (EtOH) metabolizing system able to bioactivate  alcohol to acetaldehyde and 1-hydroxyethyl radicals. These reactive  metabolites were able to covalently bind to nuclear  proteins and lipids potentially being able to provoke oxidative stress  of nuclear components. In this study, the above-mentioned possibility  was explored. Sprague Dawley male rats (125?150 g) were fed with a standard Lieber and De Carli liquid diet for 28 days. Controls were pair-fed with a diet,  in which EtOH was isocalorically  replaced with carbohydrate. The presence of a chlorzoxazone  hydroxylase activity inducible by the repetitive EtOH drinking  further suggested the presence of CYP2E1 in the highly purified  nuclei. Nuclei from EtOH-drinking rats evidenced significantly  increased susceptibility to a t-butyl hydroperoxide challenge  as detected by chemiluminescence emission, increased formation  of protein carbonyls, and decreased content of protein sulfhydryls. In contrast, no significant changes in the nuclear lipid hydroperoxides  formation or even decreases in the 8-oxo-7,8-dihydro-2-deoxyguanosine  were observed. No significant differences were observed in different  parameters of the alkaline Comet assay. In immunohistochemical  studies performed, no expression of p53 was observed in the  livers of the animals under the experimental conditions tested. Since nuclear proteins and lipids are known to play a role in  cell growth, differentiation, repair and signaling, their alterations  by either oxidative stress, or by covalent binding might be  of relevance to liver tumor promotion. Key Words: alcohol ? CYP2E1 ? ethanol ? nuclei and microsomes Toxicology and Industrial Health, Vol. 24, No. 10, 625-634 (2008)