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

  • Oxid Med Cell Longev. 2017;2017:7612182. doi: 10.1155/2017/7612182.
Peng Han  1 ,  Zhiqiang Qin  1 ,  Jingyuan Tang  2 ,  Zhen Xu  1 ,  Ran Li  1 ,  Xuping Jiang  3 ,  Chengdi Yang  1 ,  Qianwei Xing  1 ,  Xiaokang Qi  1 ,  Min Tang  1 ,  Jiexiu Zhang  1 ,  Baixin Shen  4 ,  Wei Wang  1 ,  Chao Qin  1 ,  Wei Zhang  1
Affiliations
  • 1. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, China.
  • 2. Department of Urology, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing 210029, China.
  • 3. Department of Urology, Yixing People's Hospital, Yixing 214200, China.
  • 4. Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.
PMID: 29435098 DOI: 10.1155/2017/7612182
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.

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