Potential role of empagliflozin in prevention of nephropathy in streptozotocin-nicotinamideinduced type 2 diabetes: an ultrastructural study

Abstract

Diabetic nephropathy is a serious factor in end-stage renal disease worldwide. Sodium-glucose cotransporter 2inhibitors, the most novel glucose-lowering drug, may have a nephroprotective effect by modulating blood glucose, bloodpressure and autophagy. The present work aimed to study the possible protective effect of empagliflozin in Type 2 diabeticnephropathy with special considerations to oxidative stress, fibrosis and ultrastructural modulation including autophagy.Methods: Thirty-six adult male Sprague-Dawley rats were divided into 3 groups; control, diabetic, and treatment. Type 2 diabetes was induced by pretreatment with nicotinamide followed by single low-dose of streptozotocin (40 mg/kg, i.p). The treatment group received empagliflozin (10 mg/kg/day, intragastric) for 4 weeks. At the end of 4 weeks, parameters of renal function and oxidative stress were analyzed. Kidney samples were collected for histological and ultrastructural studies.Results: Empagliflozin significantly reduced hyperglycemia, blood urea nitrogen, serum creatinine and oxidative stress whichwere elevated in the diabetic group. It also decreased renal tissue injury and fibrosis; however, did not lower the increased kidney index and glomerular size. Beside the amelioration of ultrastructure changes, empagliflozin enhanced the autophagy in renaltubular cells, indicated by increased number of autophagic vacuoles.Conclusion: Empagliflozin provided an efficient, but not complete protection against diabetic nephropathy in streptozotocin-nicotinamide-induced type 2 diabetic rat model. This effect could be related to reduction of hyperglycemia andimprovement of cellular defense mechanisms, and reduction of glucose-induced oxidative stress and autophagy.