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Melatonin attenuates acute kidney ischemia/reperfusion injury in diabetic rats by activation of the SIRT1/Nrf2/HO-1 signaling pathway
Open accessAbstract
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.
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“In a recent animal study, it has been confirmed that melatonin was able to attenuate kidney ischemia/reperfusion by the triggering SIRT1/Nrf2/HO-1 signaling pathway (Shi et al. 2019).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Shi et al. 2019
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Metadata
- Authors
- Shi, S., Lei, S., Tang, C., Wang, K., & Xia, Z.
- Affiliations
- Renmin Hospital of Wuhan University (CN)
- University of Science and Technology of China (CN)
- Corresponding author
- Xia, Zhongyuan
- Venue
- Bioscience Reports
- Publisher
- Portland Press Ltd.
- Published
- 2019-01
- Volume
- 39
- Issue
- 1
- ISSN
- 0144-8463 (ISSN-L)
- 1573-4935
- PMC
- PMC6331666
- OpenAlex
- W2906001979
- Cited by
- 135
- References
- 71
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 15 · 2023: 18 · 2022: 28 · 2021: 19 · 2020: 21 · 2019: 7
- FWCI
- 9.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Bioscience Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (WK9110000044, 81801175, 81671891)
- China Scholarship Council (201706270155)
- University of Science and Technology of China
- Fundamental Research Funds for the Central Universities (81801175, WK9110000044)
- School of Life Sciences and Biotechnology Division of Life Sciences, Korea University
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- melatonin, diabetic kidney, SIRT1, Nrf2, heme oxygenase-1, oxidative stress, apoptosis, streptozotocin-induced diabetes, EX527, SIRT1 inhibition, renal protection
- MeSH terms
- Animals, Carbazoles, Diabetes Mellitus, Experimental, Humans, Kidney, Melatonin, Signal Transduction, Reperfusion Injury, Apoptosis, Oxidative Stress, NF-E2-Related Factor 2, Rats, Heme Oxygenase-1, Sirtuin 1, Acute Kidney Injury
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