Evaluation of the Nephroprotective Effect of Dibenzazepin γ-secretase inhibitor on Renal Ischemia Reperfusion Injury in Male Rats
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1
Department of pharmacology and toxicology, Al-Mustaqbal University, College of Pharmacy, Babylon province, Iraq, Iraq
2
Department of Pharmacology and Toxicology, College of Pharmacy, University of Babylon, Iraq, Iraq
Submission date: 2025-05-12
Final revision date: 2025-10-14
Acceptance date: 2025-11-23
Publication date: 2025-12-30
Corresponding author
Zahraa I. J. Shubber
Department of pharmacology and toxicology, Al-Mustaqbal University, College of Pharmacy, Babylon province, Iraq, Iraq
Wiadomości Lekarskie 2025;(12):2725-2734
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ABSTRACT
Aim:
Aims: This study was performed to investigate the potential nephroprotective effect of Dibenzazepin on bilateral renal I/R injury in male rats.
Material and methods:
Materials and methods: Forty male rats were divided into four groups’ n=10: sham, control, DMSO, and DBZ, the sham group had a median laparotomy under anaesthesia without induction of ischemia/reperfusion; the control group underwent clamping for thirty minutes on the bilateral renal artery, after that two hours of reperfusion; the vehicle group received DMSO one hour before induction of ischemia; and the DBZ group received 2 mg/kg of DBZ one hour before ischemia. Biochemical parameters (Kidney injury molecules KIM1, IL-1β, TNF-α, F2-isoprostane, GSH, and caspase-3) were assessed by ELISA technique. Furthermore, histological changes were investigated, and the Notch signalling pathway was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).
Results:
Results: IRI caused a significant increase in renal tissues of (Kidney injury molecules KIM1, IL-1β, TNF-α, F2-isoprostane, and caspase-3) with significant decreased the level of GSH, DBZ pre-treated mitigated these effects by significant enhancing antioxidant markers and decreased inflammatory and apoptotic markers. Improving histological results and significant decrease the Notch1 and Jagged-1 gene expression in kidney tissues after renal ischemia/reperfusion damage.
Conclusions:
Conclusion: DBZ (γ-secretase inhibitor) has considerable nephroprotective benefits in renal IRI via inhibiting the Notch pathway, anti-apoptotic, antioxidant, and anti-inflammatory effect.