Kidney protective effect of sitagliptin in 5-fluorouracil-challenged rats

Abstract

The possible protective effect of sitagliptin (SIT) against nephrotoxicity induced by a single dose 5-fluorouracil (5-FU) (150 mg/kg, i.p.) was investigated in rats. SIT treatment (5 and 10 mg/kg/day, p.o.) was given for 7 days, starting 5 days before 5-FU administration. Both SIT doses caused significant reductions of serum creatinine and neutrophil gelatinase-associated lipocalin levels in rats received 5-FU. Both doses of SIT also significantly decreased malondialdehyde, tumor necrosis factor-α, interleukin-1β, nuclear factor-κB p65 (NF-κB p65), Bax/Bcl-2 ratio, and cleaved caspase-3 in kidneys of 5-FU-challenged rats. Additionally, SIT, at both doses, significantly increased renal total antioxidant capacity and nuclear factor erythroid 2related factor 2 (Nrf2) in rats received 5-FU. Besides, SIT markedly attenuated the 5-FU-induced histopathological kidney tissue injury in rats. It was concluded that SIT, at both doses, provided a significant nephroprotective effect in 5-FU-challenged rats, through its antioxidant, antiinflammatory, and antiapoptotic activities, and by modulating Nrf2 and NF-κB pathways.