Effect of dapagliflozin on paracetamol-induced hepatotoxicity and nephrotoxicity in type 2 diabetic albino rats

Introduction: paracetamol (PARA) is a worldwide antipyretic and analgesic medication. It has been extensively utilized during the last few years. PARA abuse would lead to liver and kidney injury. Dapagliflozin (DAPA)a sodium/glucose cotransporter 2 (SGLT2) inhibitor that wasapproved for treating patients with type 2 DM. In addition to its antidiabetic purpose, it has many pharmacological and biological actions, including antioxidant (radical scavenging), anti-inflammatory, and cardioprotective effects.Therefore, weaim to assess and evaluate the effect of dapagliflozin on paracetamol-induced hepatotoxicity and nephrotoxicity in rats with type 2 diabetic albino rats.Materials and Methods: eighty Wistar male rats were grouped randomly into 8 equal groups (10 rats each). Oral distilled water was given to the control group, the paracetamol group received paracetamol 0.5 g/kg dissolved in purified water orally for 4 weeks, the dapagliflozin group received dapagliflozin 1 mg/Kg daily dissolved in distilled water for 4 weeks, the paracetamol + dapagliflozin groupreceivedparacetamol and were treated with dapagliflozin.Type 2 DM was induced in rats using by intraperitoneal Streptozotocin (STZ) single injection “50mg /kg”.Rats were further subdivided into 4 groups.The control group with diabetes was given distilled water, the diabetic paracetamol group, the diabetic dapagliflozin group, and thediabetic paracetamol + dapagliflozin all received the same doses as mentioned. At the end of the experimental period, FBG, insulin, C peptide, lipid profile, liver function, fructosamine, CK-MB, TNF alpha, and IL4 were measured. Also, oxidative stress biomarkers were assessed in both kidney and liver tissues.Results: Treatment of PARA-administered rats with Dapagliflozin significantly improved FBG, insulin, C peptide, lipid profile, liver function, fructosamine, CK-MB, TNF alpha, IL4, andOxidative stress biomarkers.Conclusion: dapagliflozin has a protective effect against paracetamol-induced hepatotoxicity and nephrotoxicity.