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.
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