The effect of sitagliptin on hepatic ischemic reperfusion injury in rats

Abstract

Background: Dipeptidyl peptidase-4 (DPP4, DPPIV, CD26, EC 3.4.14.5) was found out more than four decades ago as a serine protease that severs N-terminal dipeptides from peptide substrates. DPP-4 inhibitors have been used in many animal models of lung and heart illness, in which injury was obtained by an ischemic attack followed by the following reperfusion. Here, we present the large body of experimental study that now gives irresistible evidence for the useful impact of DPP-4 targeting in ischemia/reperfusion injury. In this study, we discuss the effect of DPP-4 inhibitor (Sitagliptin) on DPP-4 expression in the rat model. Materials and Methods: We made a rat model of liver ischemia (90 min)-reperfusion (180 min), collected blood and liver samples after reperfusion. The possible inhibitory effect of Sitagliptin on DPP-4 in a rat model of hepatic ischemia-reperfusion (IR) damage was evaluated. Hepatic malondialdehyde (MDA) levels were evaluated spectrophotometrically to know the degree of oxidizing reaction in the liver. We evaluated the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the model. We used hematoxylin and eosin (H and E) staining to remark the change of liver morphologically. Results: Significantly, the expression of DPP-4 levels was declined after treatment with Sitagliptin in the IR group. MDA, TNF-α, and IL-6 levels were significantly increased in the IR group but decreased in the groups treated with Sitagliptin, 5 mg/kg. H and E staining show exact edema and necrosis were remarked in the IR group, but in the Sitagliptin pretreatment group, they were decreased. Conclusion: The study showed that pretreatment with Sitagliptin might inhibit DPP-4 activation and reduce hepatic IR damage.