MOLECULAR MECHANISMS OF THE RENAL EFFECT OF EMPAGLIFLOZIN ON LLC-PK1 CELLULAR MODEL OF DIABETIC NEPHROPATHY

Diabetic nephropathy (DN) is a major cause of chronic kidney disease and endstage renal failure. In this study, the effects of empagliflozin (SGLT2i) on cell viability and oxidative stress were investigated in the LLC-PK1 model of DN. Materials and methods: Cells were exposed to high glucose (HG30 mM) followed by 0.5 mM H2O2 and a combination of glucose and H2O2 for 24 hours. Cells were treated with various combinations of glucose and empagliflozin (100 and 500 nM) and combinations of glucose, H2O2, and empagliflozin. Colorimetric MTT assay was used to determine cell viability. Glutathione (tGSH) and TGF-β1 concentrations were measured using a spectrophotometric/microplate assay and an ELISA kit, respectively. Results: After initial exposure of cells to glucose and oxidative stress, addition of both concentrations improved cell viability and also increased the accumulation of GSH concentration (p < 0.001, p < 0.05). In addition, empagliflozin treatment caused a decrease in TGF- β1 levels in both concentrations of injured cells (p < 0.001). Conclusions: Cellular viability indicates that empagliflozin has a protective effect on renal injury. The renoprotective effect of empagliflozin is mainly mediated by the reduction of antioxidant stress and the antifibrotic properties of the drug.