Protection of NAD(P)H:quinone oxidoreductase 1 against renal ischemia/reperfusion injury in mice.
Free Radic Biol Med
; 67: 139-49, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24189322
ABSTRACT
Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage. NAD(P)H quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. The purpose of this study was to investigate whether NQO1 modulates the renal I/R injury (IRI) associated with NADPH oxidase (NOX)-derived ROS production in an animal model. We analyzed renal function, oxidative stress, and tubular apoptosis after IRI. NQO1(-/-) mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1(-/-) mice, the cellular NADPH/NADP(+) ratio was significantly higher and NOX activity was markedly higher than in those of NQO1(+/+) mice. The activation of NQO1 by ß-lapachone (ßL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I/R. Moreover, the ßL treatment significantly lowered the cellular NADPH/NADP(+) ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I/R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADP(+) modulation. These results provide convincing evidence that NQO1 activation might be beneficial for ameliorating renal injury induced by I/R.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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NAD(P)H Desidrogenase (Quinona)
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NADPH Oxidases
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Injúria Renal Aguda
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Túbulos Renais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Free Radic Biol Med
Assunto da revista:
BIOQUIMICA
/
MEDICINA
Ano de publicação:
2014
Tipo de documento:
Article