Protective effect of sitagliptin against renal ischemia reperfusion injury in rats

Abstract

This study was designed to investigate the protective effects of sitagliptin on renal damage induced by renal ischemia reperfusion (I/R) in rats. For this, rats were randomly divided into four groups (n ¼ 8): (1) sham group, in which the rats only underwent right nephrectomy; (2) right nephrectomy and left kidney ischemia (1 h) and reperfusion (24 h) group (I/R); (3) 5 mg/kg sitagliptin administrated group, per-oral once a day for two weeks; (4) 5 mg/kg sitagliptin administrated group, per-oral once a day for two weeks before left kidney I/R (n ¼ 8). Sitagliptin-treated rats that underwent renal I/R demonstrated significant decrease in the serum urea nitrogen and creatinine and also, lipid peroxidation, total oxidant status and malondialdehyde level in the renal tissue when compared to the renal I/R group. Additionally, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase and total antioxidative capacity were significantly increased after renal I/R in sitagliptin-treated rats. Our histopathological findings were in accordance with these biochemical results. In sum, in the current study all of our results indicated that sitagliptin treatment ameliorated renal damage induced by renal I/R in rats.

Head‐to‐head comparison of structurally unrelated dipeptidyl peptidase 4 inhibitors in the setting of renal ischemia reperfusion injury

“…Taken together, DPP4 inhibition did not affect the impairment of glomerular function due to IRI, measured by assessing plasma cystatin C concentrations, but did provide beneficial effects, in terms of tubular damage. One limitation of the current study, similar to the majority of previous studies (Vaghasiya et al, ; Glorie et al, ; Nuransoy et al, ; Youssef et al, ), is that no urinary parameters were investigated, which could have improved assessments of the effects of DPP4 inhibition in renal IRI on glomerular function.…”

“…Results of the current study substantiate these previous findings. In regard to beneficial effects of DPP4 inhibition on glomerular function, two studies, both investigating sitagliptin in renal IRI, also did not demonstrate any significant results (Chang et al, ; Nuransoy et al, ). Four other studies did observe significant effects of DPP4 inhibition on glomerular function (Vaghasiya et al, ; Glorie et al, ; Chen et al, ; Youssef et al, ).…”

“…To the best of our knowledge, there are six published studies and one conference abstract that investigated DPP4 inhibition in renal IRI (Vaghasiya et al, ; Daniel et al, ; Glorie et al, ; Chen et al, ; Chang et al, ; Nuransoy et al, ; Youssef et al, ). Details of these studies are summarized in Table .…”

“…Details of these studies are summarized in Table . Albeit employing a different assessment, quantitative and qualitative scoring systems, six of these studies were able to demonstrate a beneficial effect of DPP4 inhibition in renal IRI on tubular damage (Vaghasiya et al, ; Glorie et al, ; Chen et al, ; Chang et al, ; Nuransoy et al, ; Youssef et al, ). Results of the current study substantiate these previous findings.…”

Incretin-based therapy: renal effects

“…Ситаглиптин уменьшал выраженность окислитель-ного стресса и нарушения функции почек у крыс со стрептозотоциновым СД, перенесших ишемию-репер-фузию почек [41], а также у крыс с ишемией-реперфузией без СД [42,43]. Нефропротективный эффект ситаглип-тина в модели ишемии-реперфузии включал ингиби-рование воспаления в виде снижения экспрессии генов TNFα, TGFβ1, MMP-9, NF-κВ, ICAM-1 и уменьшения макрофагальной инфильтрации почек [31].…”