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Title 

Protective role of NAD(P)H: quinone oxidoreductase 1 (NQO1) in cisplatin-induced nephrotoxicity

Authors 

Gil Tae GangYong Hoon KimJung Ran NohKyoung Shim KimJ Y JungM ShongJung Hwan HwangChul Ho Lee

Publisher 

Elsevier

Issue Date 

2013

Citation 

Toxicology Letters, vol. 221, no. 3, pp. 165-175

Keywords 

β-lapachoneCisplatinNADPH oxidaseNQO1

Abstract 

Although cisplatin is widely used as an anti-cancer agent, its use is significantly limited because of its tendency to induce nephrotoxicity through poorly understood mechanisms. NAD(P)H:quinone oxidoreductase 1 (NQO1) is well known to regulate ROS generation. The purpose of this study was to investigate whether NQO1 modulates cisplatin-induced renal failure associated with NADPH oxidase (NOX)-derived ROS production in an animal model. NQO1-/- mice were treated with cisplatin (18mg/kg) and renal function, oxidative stress, and tubular apoptosis were assessed. NQO1-/- mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In accordance with these results, the cellular NADPH/NADP ratio and NOX activity were markedly increased in the kidneys of NQO1-/- mice compared to NQO1+/+ mice. In addition, activation of NQO1 by βL treatment significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis. This study demonstrates that NQO1 protects cells against renal failure induced by cisplatin, and that this effect is mediated by decreased NOX activity via cellular NADPH/NADP modulation. These results provide convincing evidence that NQO1 might be beneficial for ameliorating renal failure induced by cisplatin.

ISSN 

0378-4274

Link 

http://dx.doi.org/10.1016/j.toxlet.2013.06.239

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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