The in Vitro Cytotoxicity, Genotoxicity and Oxidative Damage Potential of Dapagliflozin on Cultured Human Blood Cells

Abstract

Objectives: Dapagliflozin (DAPA), is a potent SGLT-2 inhibitor for the treatment of patients with type 2 diabetes. DAPA has a good clinical and biological tolerance profile. However little information is available on its potential effects on cultured human blood cells. The evaluation of the in vitro cytotoxicity, genotoxicity potential and antioxidant/oxidant activity of DAPA in primary human whole blood cell cultures was aimed in this study. Materials and methods: Cell viability was measured by the MTT [3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and lactate dehydrogenase (LDH) leakage assays. The antioxidant/oxidant activity was determined by measuring the total antioxidant capacity (TAC) and total oxidative stress (TOS) levels. To assess the genotoxicity of DAPA, chromosomal aberration (CA) frequencies were determined. Results: MTT and LDH release assay exhibited that exposure to different doses of DAPA did not changed significantly the proliferation of cells. The results of TAC and TOS assays were showed that TAC level was elevated while TOS level did not altered in DAPA-treated cells. Moreover, any increase in the frequency of CA did not found on cultures blood cells. Conclusion: These data indicate that DAPA has not cytotoxic and genotoxic potential in cultured human blood cells, also, induces the increasing antioxidant activity.