Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Prevents Hepatic Injury via Liver Ischemia/reperfusion in Rats

Abstract

Background and Aim: 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 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 IRI. In our study, we discuss the effect of DPP-4 inhibitor (Sitagliptin) on DPP-4 expression in rat model. Methods: We made a rat model of liver ischemia (90min)-reperfusion (180min), collected blood and liver samples after reperfusion. The possible inhibitory effect of Sitagliptin on DPP-4 in a rat model of hepatic IR damage was evaluated. Hepatic MDA levels were evaluated spectrophotometrically to know the degree of oxidizing reaction in liver. We evaluated the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the model. We used HE staining to remark the change of liver morphologically. Results: Significantly, the expression of DPP-4 levels was declined after treatment with Sitagliptin in IR group. MDA, TNF-α and IL-6 levels were significantly increased in the IR group but decreased in the groups treated with Sitagliptin, 5mg/kg. HE staining show exact edema and necrosis were remarked in the IR group, but in the Sitagliptin pretreatment group, they were decreased. Conclusion: Our study showed that pretreatment with Sitagliptin might inhibit DPP-4 activation and reduce hepatic IR damage.