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

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Title
Protective role of NAD(P)H: quinone oxidoreductase 1 (NQO1) in cisplatin-induced nephrotoxicity
Author(s)
Gil Tae Gang; Yong Hoon KimJung Ran NohKyoung Shim Kim; J Y Jung; M Shong; Jung Hwan HwangChul Ho Lee
Bibliographic Citation
Toxicology Letters, vol. 221, no. 3, pp. 165-175
Publication Year
2013
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.
Keyword
β-lapachoneCisplatinNADPH oxidaseNQO1
ISSN
0378-4274
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.toxlet.2013.06.239
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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