Potential nephroprotective effect of dapagliflozin against renal ischemia reperfusion injury in rats via activation of autophagy pathway and inhibition of inflammation, oxidative stress and apoptosis

Abstract

Renal ischemia/reperfusion injury is a common cause of acute kidney injury (AKI), causing tissue damage, inflammation and oxidative stress. Autophagy, responsible for breakdown and recycling of cytoplasmic components. In hypoxic and ischemic renal damage, autophagy may serve as a survival strategy for the cells. Dapagliflozin has been shown to have protective effects against ischemia. Objective: The study investigates the potential nephro-protective effects of dapagliflozin on renal ischemia reperfusion injury, evaluating its antioxidant, anti-inflammatory, anti-apoptotic effects and activation of autophagy via biochemical parameters and histopathological changes in adult male rats. Material and method: In this study, twenty eight male rats weighing between 200-300g, were divided into 4 groups sham, RIRI, DMSO, Dapagliflozin pretreated groups. All groups subjected to 30 min. of ischemia then 24 h of reperfusion except sham undergo the same anesthesia and surgical procedures except for bilateral renal ischemia. Dapagliflozin 1mg/kg and DMSO was given 2 hours before the induction of ischemia. Results: The study found that blood urea and serum creatinine levels increased in RIRI and DMSO groups when compared with sham group. Renal tissue levels of IL-6, Kim-1, caspase-3, LC-3 and Akt were also elevated in RIRI while GSH levels decreased in the RIRI. Dapagliflozin group showed significant increases in GSH, LC-3 and Akt levels when compared to sham group. Dapagliflozin reduced serum urea and creatinine levels, and renal tissue levels of IL-6, Kim-1, and caspase-3 also reduced. Conclusion: Dapagliflozin significantly reduced renal damage in rat model due to its antioxidant, anti-inflammatory, anti-apoptotic, and activation autophagy.