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Melatonin Reduces Aggravation of Renal Ischemia–Reperfusion Injury in Obese Rats by Maintaining Mitochondrial Homeostasis and Integrity through AMPK/PGC-1α/SIRT3/SOD2 Activation

Authors :
Anongporn Kobroob
Aphisek Kongkaew
Orawan Wongmekiat
Source :
Current Issues in Molecular Biology, Vol 45, Iss 10, Pp 8239-8254 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

This study examined the potential benefits of melatonin against renal ischemia and reperfusion (IR) injury in obesity and explored the underlying mechanisms. Obesity was induced in Wistar rats by feeding a high-fat diet for 16 weeks. Three obese groups that underwent renal IR induction (30-min renal ischemia followed by 24-h reperfusion) were randomly assigned to receive melatonin at ischemic onset, reperfusion onset, or pretreatment for 4 weeks before IR induction. Groups of vehicle-treated obese and normal-diet-fed rats that underwent sham or IR induction were also included in the study. The results showed that renal functional and structural impairments after IR incidence were aggravated in obese rats compared to normal-diet-fed rats. The obese-IR rats also exhibited oxidative stress, mitochondrial dysfunction, apoptosis, and mitochondrial dynamics and mitophagy imbalances, which were all considerably improved upon melatonin treatment, irrespective of the treatment time. This study suggests the prophylactic and therapeutic efficacy of melatonin in IR-induced acute kidney injury (AKI) in obese individuals, which may improve the prognosis of AKI in these populations. The benefits of melatonin are likely mediated by the modification of various signaling molecules within the mitochondria that maintain mitochondrial redox balance and lead to the protection of mitochondrial homeostasis and integrity.

Details

Language :
English
ISSN :
14673045 and 14673037
Volume :
45
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Current Issues in Molecular Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.7e78c4ba9b884bf5a1cc87d5dae299b9
Document Type :
article
Full Text :
https://doi.org/10.3390/cimb45100520