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Titolo:
An alcoholic binge causes massive degradation of hepatic mitochondrial DNAin mice
Autore:
Mansouri, A; Gaou, I; De Kerguenec, C; Amsellem, S; Haouzi, D; Berson, A; Moreau, A; Feldmann, G; Letteron, P; Pessayre, D; Fromenty, B;
Indirizzi:
Hop Beaujon, INSERM, U481, F-92118 Clichy, France Hop Beaujon Clichy France F-92118 , INSERM, U481, F-92118 Clichy, France Hop Beaujon, Ctr Claude Bernard Rech Hepatites Virales, F-92118 Clichy, France Hop Beaujon Clichy France F-92118 atites Virales, F-92118 Clichy, France Fac Med Xavier Bichat, INSERM, U327, Paris, France Fac Med Xavier Bichat Paris France Bichat, INSERM, U327, Paris, France
Titolo Testata:
GASTROENTEROLOGY
fascicolo: 1, volume: 117, anno: 1999,
pagine: 181 - 190
SICI:
0016-5085(199907)117:1<181:AABCMD>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
ISOLATED RAT HEPATOCYTES; OXIDATIVE DAMAGE; MICROVESICULAR STEATOSIS; LIPID-PEROXIDATION; BETA-OXIDATION; APURINIC SITES; ETHANOL; CHAIN; ACID; GENERATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Fromenty, B Hop Beaujon, INSERM, U481, F-92118 Clichy, France Hop BeaujonClichy France F-92118 81, F-92118 Clichy, France
Citazione:
A. Mansouri et al., "An alcoholic binge causes massive degradation of hepatic mitochondrial DNAin mice", GASTROENTY, 117(1), 1999, pp. 181-190

Abstract

Background & Aims: Ethanol causes oxidative stress in the hepatic mitochondria of experimental animals and mitochondrial DNA deletions in alcoholics. We postulated that ethanol intoxication may cause mitochondrial DNA strandbreaks. Methods: Effects of an intragastric dose of ethanol (5 g/kg) on hepatic mitochondrial DNA levels, structure, and synthesis were determined byslot blot hybridization, Southern blot hybridization, and in vivo [H-3]thymidine incorporation, respectively. Results: Two hours after ethanol administration, ethane exhalation (an index of lipid peroxidation) increased by 133%, although hepatic lipids were unchanged. Mitochondrial DNA was depletedby 51%. Its supercoiled form disappeared, whereas linearized forms increased. Long polymerase chain reaction evidenced lesions blocking polymerase progress on the mitochondrial genome. Mitochondrial transcripts decreased. Subsequently, [H-3]thymidine incorporation into mitochondrial DNA increased, and mitochondrial DNA levels were restored. In contrast, nuclear DNA was not fragmented and its [H-3]thymidine incorporation was unchanged. Liver ultrastructure only showed inconstant mitochondrial lesions. Ethanol-induced mitochondrial DNA depletion was prevented by 4-methylpyrazole, an inhibitor of ethanol metabolism, and attenuated by melatonin, an antioxidant. Conclusions: After an alcoholic binge, ethanol metabolism causes oxidative stress and hepatic mitochondrial DNA degradation in mice. DNA strand breaks may be involved in the development of mitochondrial DNA deletions in alcoholics.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 06:41:48