Evaluation of the protective effect of dapagliflozin in preventing Amphotericin-B induced nephrotoxicity in an experimental rat model

Objective: Amphotericin B deoxycholate (AmBD) is a broad-spectrum antifungal agent and one of the cornerstone treatments for various systemic fungal infections. One of the most significant side effects limiting its use is nephrotoxicity. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are antidiabetic drugs with renal protective potential beyond glycemic control. In this study, we investigated the potential renoprotective effects of dapagliflozin, an SGLT-2 inhibitor, on an AmBD-induced nephrotoxicity model in rats using histopathological and biochemical analyses. Materials and Methods: A total of 32 Wistar albino rats were divided into four groups, each containing 8 rats: (1) Control group (received isotonic saline 15 mg/kg/day), (2) AmBD group (received a single dose of AmBD, 50 mg/kg intraperitoneally), (3) Dapagliflozin group (received dapagliflozin 10 mg/kg/day orally via gavage for 7 days), and (4) AmBD + Dapagliflozin group (received dapagliflozin 10 mg/kg/day via gavage for 7 days along with a single dose of AmBD, 50 mg/kg i.p). On the 8th day, bilateral nephrectomy was performed on all rats. Serum samples were analyzed for markers of oxidative stress (MDA, MPO, NO, and TOS), apoptotic mediators (BAX, BCL-2, and Caspase-3), the antioxidant system (TAS, GPx, CAT, and SOD), and kidney function (BUN and creatinine). Results: In the AmBD group, we observed significant acute kidney injury (AKI), evident from both histopathological findings and elevated serum creatinine and BUN levels. Administration of dapagliflozin reduced these markers of kidney damage. When evaluating other biochemical parameters, the co-administration of dapagliflozin with AmBD did not yield significant changes in oxidative stress markers (TOS, MDA, MPO, and NO) or apoptotic mediators (BAX, BCL-2, and Caspase-3). However, some antioxidant system markers (CAT and SOD) showed favorable increases with dapagliflozin treatment. Conclusion: Dapagliflozin alleviated AmBD-induced kidney injury and demonstrated a renoprotective effect. We can conclude that dapagliflozin does not exert this effect by reducing oxidative stress and apoptosis. Further studies with larger sample sizes, extended evaluation periods, and investigations targeting different systems and specific molecules are needed to clarify the renoprotective mechanisms of dapagliflozin.