Protective effects of bexagliflozin on renal function in a rat model of ischemia-reperfusion injury; an experimental animal study

Abstract

Introduction: Ischemia-reperfusion injury (IRI) is a significant clinical challenge that often leads to acute kidney injury (AKI), adversely affecting renal function and patient outcomes. Recent advancements in pharmacotherapy have highlighted the potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors in providing renal protection. Objectives: This study aimed to investigate the protective effects of bexagliflozin on renal function in a rat model subjected to IRI. Materials and Methods: In an experimental study, 28 male rats, weighing between 200-300 g, were utilized in this experimental study and divided into four distinct groups. The sham group underwent identical anesthesia and surgical procedures without the induction of ischemia. The IRI group experienced 30 minutes of bilateral renal ischemia followed by 24 hours of reperfusion. The dimethyl sulfoxide (DMSO) group, serving as a vehicle for bexagliflozin, received an oral dose two hours before the ischemia induction and subsequently underwent the same reperfusion protocol. In the bexagliflozin pretreated group, rats were administered bexagliflozin at a dosage of 3 mg/kg orally two hours before ischemia induction, followed by 30 minutes of bilateral renal ischemia and 24 hours of reperfusion. After the reperfusion period, all rats were subjected to a laparotomy to collect blood and kidney samples, including urea, creatinine, interleukin-6 (IL-6), Akt, glutathione (GSH), caspase, light chain 3-B (LC3-B), kidney injury molecules-1 (KIM-1), and histopathological renal tubular injury. Results: The study findings indicated that both the IRI and IRI+DMSO groups experienced significant renal impairment compared to the sham group, as evidenced by elevated levels of serum urea, creatinine, caspase, Akt, LC3-B, KIM-1, and IL-6, alongside decreased GSH levels. In contrast, the IRI + bexagliflozin treatment group demonstrated notable protective effects against renal injury, reflected in lower levels of these parameters and reduced renal tubular injury scores compared to the IRI and IRI+DMSO groups. Furthermore, bexagliflozin was associated with a smaller increase in GSH levels relative to the other groups, underscoring its potential therapeutic role in alleviating renal damage linked to IRI. Conclusion: Bexagliflozin demonstrated promising protective effects against renal injury, as evidenced by lower levels of injury markers and reduced renal tubular damage. These findings suggest that bexagliflozin may serve as a viable therapeutic option for mitigating renal damage associated with IRI, warranting further investigation into its clinical applications.