A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/reperfusion in rats

Acute kidney injury (AKI) is associated with high mortality resulting from extra-renal organ damage, particularly the heart. The present study aimed to investigate the protective effect of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, against renal and remote cardiac damage induced by ischemia/reperfusion (IR), a leading cause of AKI. In this attempt, we compared the effects of sitagliptin to furosemide, a loop diuretic. Furosemide is commonly used clinically in AKI however, there is a lack of evidence regarding its beneficial effects in AKI. In addition, the combined administration of both drugs was also investigated. Ischemia was induced in anesthetized male Wistar rats by occluding both renal pedicles for 30min followed by reperfusion for 24h. Sitagliptin (5mgkg−1), furosemide (245mgkg−1) or their combination were administered orally at 5h post-IR and 2h before euthanasia. Administration of sitagliptin or furosemide ameliorated renal and cardiac deterioration induced by renal IR. This was manifested as significant reduction of serum creatinine, urea, cystatin c, creatine kinase-MB, cardiac troponin-I and lactate dehydrogenase (P