Melatonin attenuates acute kidney ischemia/reperfusion injury in diabetic rats by activation of the SIRT1/Nrf2/HO-1 signaling pathway

Author:

Shi Si1,Lei Shaoqing1,Tang Chaoliang12ORCID,Wang Kai1,Xia Zhongyuan1ORCID

Affiliation:

1. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China

2. Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China

Abstract

Abstract Background and aims: Diabetic kidney is more sensitive to ischemia/reperfusion (I/R) injury, which is associated with increased oxidative stress and impaired nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Melatonin, a hormone that is secreted with the rhythm of the light/dark cycle, has antioxidative effects in reducing acute kidney injury (AKI). However, the molecular mechanism of melatonin protection against kidney I/R injury in the state of diabetes is still unknown. In the present study, we hypothesized that melatonin attenuates renal I/R injury in diabetes by activating silent information regulator 2 associated protein 1 (SIRT1) expression and Nrf2/HO-1 signaling. Methods: Control or streptozotocin (STZ)-induced Type 1 diabetic rats were treated with or without melatonin for 4 weeks. Renal I/R injury was achieved by clamping both left and right renal pedicles for 30 min followed by reperfusion for 48 h. Results: Diabetic rats that were treated with melatonin undergoing I/R injury prevented renal injury from I/R, in aspects of the histopathological score, cell apoptosis, and oxidative stress in kidney, accompanied with decreased expressions of SIRT1, Nrf2, and HO-1 as compared with those in control rats. All these alterations were attenuated or prevented by melatonin treatment; but these beneficial effects of melatonin were abolished by selective inhibition of SIRT1 with EX527. Conclusion: These findings suggest melatonin could attenuate renal I/R injury in diabetes, possibly through improving SIRT1/Nrf2/HO-1 signaling.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry,Biophysics

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