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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 7612182, 15 pages
https://doi.org/10.1155/2017/7612182
Research Article

RTA-408 Protects Kidney from Ischemia-Reperfusion Injury in Mice via Activating Nrf2 and Downstream GSH Biosynthesis Gene

1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, China
2Department of Urology, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing 210029, China
3Department of Urology, Yixing People’s Hospital, Yixing 214200, China
4Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China

Correspondence should be addressed to Wei Zhang

Received 14 July 2017; Revised 18 October 2017; Accepted 5 November 2017; Published 24 December 2017

Academic Editor: Hongbing Liu

Copyright © 2017 Peng Han et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Acute kidney injury (AKI) induced by ischemia-reperfusion is a critical conundrum in many clinical settings. Here, this study aimed to determine whether and how RTA-408, a novel oleanane triterpenoid, could confer protection against renal ischemia-reperfusion injury (IRI) in male mice. Mice treated with RTA-408 undergoing unilateral ischemia followed by contralateral nephrectomy had improved renal function and histological outcome, as well as decreased apoptosis, ROS production, and oxidative injury marker compared with vehicle-treated mice. Also, we had found that RTA-408 could strengthen the total antioxidant capacity by increasing Nrf2 nuclear translocation and subsequently increased Nrf2 downstream GSH-related antioxidant gene expression and activity. In vitro study demonstrated that GSH biosynthesis enzyme GCLc could be an important target of RTA-408. Furthermore, Nrf2-deficient mice treated with RTA-408 had no significant improvement in renal function, histology, ROS production, and GSH-related gene expression. Thus, by upregulating Nrf2 and its downstream antioxidant genes, RTA-408 presents a novel and potential approach to renal IRI prevention and therapy.