Maresin 1 mitigates renal ischemia/reperfusion injury in mice via inhibition of the TLR4/MAPK/ NF-κB pathways and activation of the Nrf2 pathway
Authors Qiu Y, Wu Y, Zhao H, Sun H, Gao S
Received 25 September 2018
Accepted for publication 29 January 2019
Published 20 February 2019 Volume 2019:13 Pages 739—745
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Sukesh Voruganti
Yun Qiu, Yichen Wu, Hongmei Zhao, Hong Sun, Sumin Gao
Department of Emergency Medicine, The Affiliated Huaian No 1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu Province, China
Background: Inflammation and oxidative stress play a crucial role in the pathogenesis of renal ischemia/reperfusion injury (IRI). Maresin 1 (MaR1), which has shown strong anti-inflammatory and antioxidant effects, was recently reported to have protective properties in several different animal models.
Aim: The objectives of our study were to determine whether MaR1 alleviates renal IRI and to identify the underlying mechanisms.
Materials and methods: The mouse model in this study was induced by ischemia of the left kidney for 45 minutes and by nephrectomy of the right kidney. All mice were intravenously injected with a vehicle or MaR1. Renal histopathologic changes, function, proinflammatory cytokines, and oxidative stress were assessed. The expression of proteins was measured by Western blot.
Results: The results indicated that MaR1 markedly protected against renal IRI. The protective effects were accompanied by the reduction of histologic changes and reduction of renal dysfunction. Meanwhile, MaR1 remarkably mitigated renal IRI-induced inflammation and oxidative stress. In addition, our results showed that MaR1 significantly inhibited the expression of TLR4 and the expression of phosphorylated Erk, JNK, and P38. Furthermore, MaR1 decreased the nuclear translocation of NF-κB and increased the nuclear translocation of Nrf2.
Conclusion: MaR1 protects against renal IRI by inhibiting the TLR4/MAPK/NF-κB pathways, which mediate anti-inflammation, and by activating the Nrf2 pathway, which mediates antioxidation.
Keywords: renal ischemia/reperfusion injury, Maresin 1, TLR4, MAPK, NF-κB, Nrf2
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