Evaluation of the Nephroprotective Effect of Dibenzazepin γ-secretase inhibitor on Renal Ischemia Reperfusion Injury in Male Rats

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.