Effect of Saxagliptin on Cisplatin-Induced Nephrotoxicity in Rats

Abstract

Background: Nephrotoxicity is the most common side effect of cisplatin, cisplatin as a chemotherapy is used widely in the treatment of solid tumors so nephro-protection is highly recommended. Saxagliptin is a new antidiabetic drug that show great effect in improving the glycemic profile of patient with type 2 diabetes mellitus. Aim: The current study investigated the renoprotective effect of saxagliptin (12.5mg/kg, IP) against cisplatin-induced nephrotoxicity in rats. Methods: Twenty-four adult male albino rats were randomly assigned to four groups, each group contained 6 rats. Results: Saxagliptin administration for 14 days revealed a significant nephroprotection against cisplatin-induced nephrotoxicity manifested by improvement in kidney function, significant decrease in the serum urea and creatinine, albuminuria, and albumin/creatinine ratio, while significant increase in the urine volume, and urine creatinine. Also, kidney contents of MDA, TNFα and DPP4 enzyme level significantly declined with significant increase in GSH, catalase concentration compared to cisplatin treated group. Also, significant histopathological improvement occurred. Conclusion: saxagliptin has anti oxidative stress effects and anti-inflammatory properties through long-lasting inhibition of renal membrane bound DPP4 enzyme.

Keywords

• saxagliptin
• cisplatin
• nephrotoxicity
• nephroprotection, catalase, reduced glutathione, malondialdehyde, dpp4 enzyme, tnf alpha, histopathology