POSSIBLE AMELIORATIVE EFFECT OF SITAGLIPTIN ON CISPLATIN-INDUCED NEPHROTOXICITY IN ALBINO RATS
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Cisplatin chemotherapeutic efficacy in cancer therapy is limited by its nephrotoxicity. Sitagliptin, an orally available dipeptidyl peptidase-4 (DPP-4) inhibitor developed to be used as a once daily treatment for type 2 diabetes mellitus (T2DM), and could attenuate diabetic nephropathy in rats. The ameliorative effect of sitagliptin was studied on cisplatin-induced nephrotoxicity in albino rats. Twenty four male albino rats were classified into 4 equal groups each containing 6 rats. The Pt group involved normal control rats receiving saline, the 21th group involved untreated cisplatin-induced nephrotoxicity rats (by 6 mg/kg), the rgroup involved rats receiving sitagliptin (10 mg/kg/day) for 6 weeks, and the 4" group involved rats treated by sitagliptin (10 mg/kg/day) for 6 weeks after induction of nephrotoxicity by cisplatin. Serum urea and creatinine levels, intra-renal reduced glutathione (GSH) level, tumor necrosis factor-a (TNF- a) level, renal blood flow changes and histopathological examination of the kidney were studied. The current work revealed that treatment with oral sitagliptin in male albino rats after induction of nephrotoxicity by cisplatin resulted in a significant improvement of cisplatin-induced nephrotoxicity. These results evident by a significant (p<0.05) reduction in serum urea, serum creatinine and tumor necrosis factor-a (TNF- a) levels by 49.2%, 50% and 58.1% respectively and a significant increase in renal blood flow and intrarenal reduced glutathione (0511) level by >100% and 17.9% respectively compared to the untreated cisplatin group. However, these results still highly significant as compared to the normal control and sitagliptin treated group. In addition, there was a significant improvement of the histopathological examination of the kidney. Thus, sitagliptin can ameliorate nephrotoxicity induced by cisplatin.