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

Year 2019, Volume: 13 Issue: 3, 137 - 148, 31.12.2019

Hagar A. Hashish , Marwa Abd El-kader

Abstract

Objectives: Diabetic nephropathy is a serious factor in end-stage renal disease worldwide. Sodium-glucose cotransporter 2
inhibitors, the most novel glucose-lowering drug, may have a nephroprotective effect by modulating blood glucose, blood
pressure and autophagy. The present work aimed to study the possible protective effect of empagliflozin in Type 2 diabetic
nephropathy 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 which
were 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 renal
tubular 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 and
improvement of cellular defense mechanisms, and reduction of glucose-induced oxidative stress and autophagy.

Keywords

Diabetes, Nephropathy, Autophagy, empagliflozin

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