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Titolo:
Role of oxidative stress and glutathione in busulfan toxicity in cultured murine hepatocytes
Autore:
DeLeve, LD; Wang, XD;
Indirizzi:
Univ So Calif, Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA Univ So Calif Los Angeles CA USA 90033 ver Dis, Los Angeles, CA 90033 USA Univ So Calif, Sch Med, Dept Med, Ctr Liver Dis Res, Los Angeles, CA 90033USA Univ So Calif Los Angeles CA USA 90033 Dis Res, Los Angeles, CA 90033USA
Titolo Testata:
PHARMACOLOGY
fascicolo: 3, volume: 60, anno: 2000,
pagine: 143 - 154
SICI:
0031-7012(2000)60:3<143:ROOSAG>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; BONE-MARROW TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; CROSS-LINKING; HUMAN LIVER; CELLS; DISULFIDES; REGIMENS; THIOLS; RAT;
Keywords:
busulfan; glutathione; oxidative stress; hepatic veno-occlusive disease; hepatitis, toxic; glutathione transferase; cell, cultured;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: DeLeve, LD Univ So Calif, Sch Med, Div Gastrointestinal & Liver Dis, Hlth Sci Campus,2011 Zonal Ave,HMR 603, Los Angeles, CA 90033 USA Univ So Calif Hlth Sci Campus,2011 Zonal Ave,HMR 603 Los Angeles CA USA 90033
Citazione:
L.D. DeLeve e X.D. Wang, "Role of oxidative stress and glutathione in busulfan toxicity in cultured murine hepatocytes", PHARMACOL, 60(3), 2000, pp. 143-154

Abstract

This study examines busulfan metabolism. Busulfan given in vivo or in vitro decreased hepatocyte glutathione (GSH) by 60 and 50%, respectively. In vitro, busulfan toxicity was prevented by glutathione S-transferase inhibitors or by antioxidants and led to increased production of oxidized GSH and thiobarbituric acid reactive substances. 'Rescue' from toxicity by GSH precursors was prevented by N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU). Depletion of GSH exacerbated toxicity. In GSH depleted hepatocytes, busulfan decreased GSH by 95% and BCNU did not prevent rescue by GSH precursors. Conclusions: (1) In hepatocytes with normal GSH: busulfan toxicity requires GSH conjugation, does not cause profound GSH depletion and is mediated by oxidativestress. We postulate that a GSH conjugate promotes oxidative stress. (2) In GSH-depleted hepatocytes: busulfan profoundly depletes GSH; toxicity is mediated by oxidative stress and is prevented by restoring GSH levels; cell death may be due to unopposed endogenous oxidative stress. Copyright (C) 2000 S. Karger AG, Basel.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/02/20 alle ore 17:39:28