Effects of empagliflozin on oxidative stress and endothelial dysfunction in STZ-induced Type 1 diabetic rat

Background, methods: In diabetes, cardiovascular complications are associated with endothelial dysfunction and oxidative stress. Empagliflozin, as a selective sodium glucose cotransporter (SGLT) 2 inhibitor in clinical development, offers a promising novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with Empagliflozin could improve endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated oxidative stress. Type I diabetes in Wistar rats was induced by an i.v. injection of streptozotocin (60 mg/kg). One week after injection Empagliflozin was administered via drinking water for 7 weeks.

Results: Treatment with Empagliflozin (10 and 30 mg/kg/d), showed reduction of blood glucose and a normalization of endothelial dysfunction (aortic rings) in diabetic rats and a reduced oxidative stress in aortic vessels (dihydroethidine staining), in blood (phorbol ester/zymosan A-stimulated chemiluminescence) compared to control. Additionally, the higher NADPH-oxidase activity in heart tissue of diabetic animals was normalized by SGLT2 inhibitor therapy.

Conclusion: In this study we could demonstrate that Empagliflozin improves hyperglycemia and prevents the development of endothelial dysfunction and oxidative stress in type 1 diabetic rats. Future studies will investigate the underlying mechanisms of these antioxidant and anti-inflammatory effects with special emphasis on the activity of NADPH oxidase and the prevention of uncoupling of the nitric oxide synthase, which contributes to cardiovascular complications.