| Deleterious effects induced by oxidative stress in liver nuclei from rats receiving an alcohol-containing liquid diet. | |
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MedLine Citation:
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PMID: 19141567 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 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. |
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Authors:
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M I Díaz Gómez; S L Fanelli; A M A Delgado de Layño; F M Bietto; J A Castro; G D Castro |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Toxicology and industrial health Volume: 24 ISSN: 0748-2337 ISO Abbreviation: Toxicol Ind Health Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2009-01-14 Completed Date: 2009-04-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8602702 Medline TA: Toxicol Ind Health Country: England |
Other Details:
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Languages: eng Pagination: 625-34 Citation Subset: IM |
Affiliation:
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Centro de Investigaciones Toxicológicas, CITEFA/CONICET, Buenos Aires, Argentina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Nucleus / metabolism* Chlorzoxazone / analogs & derivatives, metabolism Comet Assay Cytochrome P-450 CYP2E1 / metabolism Data Interpretation, Statistical Deoxyguanosine / analogs & derivatives, analysis Ethanol / administration & dosage* Hepatocytes / cytology, metabolism Immunohistochemistry Lipid Peroxidation / drug effects Liver / chemistry, cytology, metabolism* Male Microsomes, Liver / chemistry, metabolism Mixed Function Oxygenases / metabolism Oxidative Stress / drug effects* Protein Carbonylation / drug effects Rats Rats, Sprague-Dawley Sulfhydryl Compounds / metabolism Tumor Suppressor Protein p53 tert-Butylhydroperoxide / metabolism |
| Chemical | |
Reg. No./Substance:
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0/8-hydroxy-2'-deoxyguanosine; 0/Sulfhydryl Compounds; 0/Tumor Suppressor Protein p53; 1750-45-4/6-hydroxychlorzoxazone; 64-17-5/Ethanol; 75-91-2/tert-Butylhydroperoxide; 95-25-0/Chlorzoxazone; 961-07-9/Deoxyguanosine; EC 1.-/Mixed Function Oxygenases; EC 1.14.14.1/Cytochrome P-450 CYP2E1 |
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