Autophagy and Oxidative Balance Mediate the Effect of Carvedilol and Glibenclamide in a Rat Model of Renal Ischemia-Reperfusion Injury

Amany Elfakhrany; Reda Abo Elfath Ahmed Abo-Elsoud; Heba Mohamed Abd El Kareem; Rehab Monir Samaka; Safa Reyad Elfiky

doi:10.3889/oamjms.2022.10125

Authors

Amany Elfakhrany Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, Shibin Al Kawm, Egypt
Reda Abo Elfath Ahmed Abo-Elsoud Department of Clinical Physiology, Faculty of Medicine, Menoufia University, Shibin Al Kawm, Egypt
Heba Mohamed Abd El Kareem Department of Medical Biochemistry, Faculty of Medicine, Benha University, Banha, Egypt; Department of Medical Biochemistry, Faculty of Medicine, Mutah University, Mu’tah, Jordan
Rehab Monir Samaka Department of Pathology, Faculty of Medicine, Menoufia University, Shibin Al Kawm, Egypt
Safa Reyad Elfiky Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, Shibin Al Kawm, Egypt

DOI:

https://doi.org/10.3889/oamjms.2022.10125

Keywords:

Kidney, Ischemia-reperfusion injury, Autophagy, Carvedilol, Glibenclamide

Abstract

BACKGROUND: Reactive oxygen species and cytokines are the main players in the development of renal ischemia-reperfusion (I/R) injury.

AIM: The current study aimed to evaluate the effects of carvedilol and/or glibenclamide and the interaction between autophagy and oxidative stress.

METHODS: 50 male rats were divided into five groups: Control, IR injury (IRI), carvedilol pretreated, glibenclamide pretreated, and combined carvedilol and glibenclamide pretreated. Measurements of renal blood flow (RBF), creatinine clearance, serum blood urea nitrogen (BUN), histopathological, and immunohistochemical evaluation of autophagy marker Becl-1 in the rat kidney were performed. Beclin-1and light chain 3 (LC3) Mrna expression was detected by real time polymerase chain reaction.

RESULTS: IRI was associated with significant increases in BUN, tumor necrosis factor-alpha, nuclear factor κB, and histo (H) score value of Becl-1. However, there was a significant decrease in RBF, creatinine clearance, and glutathione peroxidase compared to the control group. There was significant increase in Beclin-1 and LC3 mRNA gene expression in carvedilol, glibenclamide, and combined treatment groups as compared to IRI and control groups. Combination of carvedilol and glibenclamide significantly restored IRI changes when compared with the other pretreated groups.

CONCLUSION: This study suggests that carvedilol and glibenclamide are promising reno-protective drugs to reduce renal injury induced by I/R through their antioxidant and autophagy stimulation.

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