• Gil-Tae Gang, Jung Hwan Hwang, Yong-Hoon Kim, Jung-Ran Noh, Kyoung-Shim Kim, Jin Young Jeong, Dae Eun Choi, Kang Wook Lee, Ju-Young Jung, Minho Shong, and Chul-Ho Lee.
• Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea.
• Free Radic. Biol. Med. 2014 Feb 1;67:139-49.

UnlabelledIschemia/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)Hquinone 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 β-lapachone (βL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I/R. Moreover, the βL 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.© 2013 Elsevier Inc. All rights reserved.

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