Notch inhibitor mitigates renal ischemia-reperfusion injury in diabetic rats

Diabetes mellitus can exacerbate renal ischemia-reperfusion (I/R) injury (RI/RI) in diabetic rats. Previous studies have shown that Notch signaling is involved in renal disorders. The aim of the present study was to evaluate the protective effect of the Notch inhibitor γ-secretase N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) on RI/RI in a streptozocin (STZ)-induced diabetic rat model. STZ-induced diabetic rats were randomly grouped for different treatments. Cisplatin was used to trigger the Notch signaling pathway and the animals were preconditioned with DAPT to block the signaling pathway. Renal function, oxidative stress and inflammatory factors were examined. DAPT-treated diabetic rats demonstrated mitigated renal injury and function, antioxidative activity was significantly improved and HIF-1a was upregulated. Notch inhibitor DAPT is a potential therapeutic target to improve the outcome of RI/RI in STZ-induced diabetic rats in part via the regulation of anti-oxidation and HIF-1a.