Protective effect of Saxagliptin on diabetic rats with renal ischemia reperfusion injury by targeting oxidative stress and mitochondrial apoptosis pathway through activating Nrf-2/HO-1 signaling

Abstract

Oxidative stress and apoptosis play vital role in diabetic rats suffering from renal ischemia reperfusion injury (IRI). As a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, Saxagliptin(SAX)has been confirmed in the regulation of inflammation and apoptosis by targeting Nrf-2/HO-1signalling. The study was designed to explore the efficacy and potential mechanisms of SAX on inflammation and apoptosis for treating of IRI in diabetic rats. Through testing the expressions of Nrf-2, HO-1, Cleaved-Caspase9, Cleaved-Caspase3, Bax, BCL-2, Bak, Apaf-1, cytochrome C (Cytc), Cystatin C (CysC), β2-microglobulin (β2-MG), creatinine (Cr), urea nitrogen (BUN), TUNEL and pathological morphology, the effects of SAX on IRI diabetic rats have been investigatedg. The results has displayed SAX treatment significantly attenuate the cell apoptosis and pathological damage of kidney as well as lessening the expression of cleaved-caspase-9, cleaved-caspase3, Bax, cytoplasmic-Cytc, MDA, Bak, and Apaf-1 molecules, and the contents of ROS, Cr, CysC, β2-MG, and BUN. Furthermore, SAX therapy also increased the expression of Nrf-2, BCL-2, HO-1 and mitochondrial cytochrome Cytc, and enhanced the activity of SOD, CAT and GPx. Therefore, our study has indicated that SAX treatment alleviated IRI in diabetic rats by suppressing oxidative stress and mitochondrial apoptotic pathways by activating the Nrf-2/HO-1 signaling.