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Titolo:
Doxorubicin-induced persistent oxidative stress to cardiac myocytes
Autore:
Zhou, SY; Palmeira, CM; Wallace, KB;
Indirizzi:
Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, Duluth, MN 55812 USA Univ Minnesota Duluth MN USA 55812 ochem & Mol Biol, Duluth, MN 55812 USA Univ Minnesota, Sch Med, Toxicol Grad Program, Duluth, MN 55812 USA Univ Minnesota Duluth MN USA 55812 col Grad Program, Duluth, MN 55812 USA Univ Coimbra, Dept Zool, Ctr Neurosci & Cell Biol, P-3000 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3000 Cell Biol, P-3000 Coimbra, Portugal
Titolo Testata:
TOXICOLOGY LETTERS
fascicolo: 3, volume: 121, anno: 2001,
pagine: 151 - 157
SICI:
0378-4274(20010519)121:3<151:DPOSTC>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
MITOCHONDRIAL-DNA; INDUCED CARDIOMYOPATHY; HEART-MITOCHONDRIA; HYDROGEN-PEROXIDE; GENE-EXPRESSION; BOVINE HEART; MOUSE HEART; COMPLEX III; RAT-HEART; ADRIAMYCIN;
Keywords:
cardiac myocytes; doxorubicin; glutathione protein-thiol; reactive oxygen species;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Wallace, KB Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, Duluth, MN 55812 USA Univ Minnesota Duluth MN USA 55812 Biol, Duluth, MN 55812 USA
Citazione:
S.Y. Zhou et al., "Doxorubicin-induced persistent oxidative stress to cardiac myocytes", TOX LETT, 121(3), 2001, pp. 151-157

Abstract

We recently reported a cardioselective and cumulative oxidation of cardiacmitochondrial DNA (mtDNA) following subchronic administration of doxorubicin to rats. The mtDNA adducts persist for up to 5 weeks after cessation of doxorubicin treatment. Since the evidence suggests that this persistence ofmtDNA adducts cannot be attributed to a lack of repair and replication, weinvestigated whether it might reflect a long-lasting stimulation of free radical-mediated adduct formation. Male Sprague-Dawley rats received weekly s.c. injections of either doxorubicin (2 mg:kg) or an equivalent volume of saline. Cardiac myocytes isolated from rats Following 6 weekly injections of doxorubicin expressed a much higher rare of reactive oxygen species (ROS)Formation compared to saline controls. This higher rate of ROS Formation persisted for 5 weeks following the last injection. Associated with this wasa persistent depression of GSH in heart tissue, while protein-thiol content was not markedly altered. These data suggest that the accumulation and persistence of oxidized mtDNA may be due, not to the stability of the adducts. but to some as yet undefined toxic lesion that causes long-lasting stimulation of ROS generation by doxorubicin. This persistent generation of ROS may contribute to the cumulative and irreversible cardiotoxicity observed clinically with the drug. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 13:02:45