In Vitro Cytotoxic, Genotoxic, Embryotoxic and Oxidative Damage Potentials by Empagliflozin

Abstract: Empagliflozin (EMPA) is a potent, competitive and selective sodium glucose cotransporter-2 (SGLT-2) inhibitor that ameliorates blood glucose with the insulin-independent manner. EMPA reduces weight and blood pressure of patients with type 2 diabetes mellitus (T2DM) without developing hypoglycemic risk. To the best of our knowledge, its safety profiling has not been evaluated on human blood cell cultures yet. Again, the embryotoxicity potential by EMPA is still unclear. Therefore, in this investigation we aimed to evaluate the in vitro cytotoxic, genotoxic and embryotoxic damage potential as well as antioxidative/oxidative effects by EMPA in cultured human blood and human pluripotent embryonal carcinoma NT2 cells for the first time. Cell cultures (n = 5) were exposed to different concentrations ranging from 3.25 to 100 mg/L of EMPA for 48 and 72 h. Cell viability was measured by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays. The alterations in antioxidant/oxidant activity were monitored via measuring the total antioxidant capacity (TAC) and total oxidative stress (TOS) levels. For evaluating the genotoxicity of EMPA chromosomal aberration (CA) assay was performed. The present results revealed that EMPA did not induce cytotoxic or genotoxic damage on healthy human blood cells. Moreover, EMPA exerted non-embryotoxic property and supported antioxidative capacity and decreased the oxidative stress in cultured human blood cells. Our results supported the safe and advantageous use of EMPA for the treatment of T2DM.