EVALUATION OF CYTOTOXIC AND GENOTOXIC EFFECTS OF SAXAGLIPTIN

Saxagliptin (SAX) is an oral drug that is a hypoglycemic (between an anti-diabetic agent) dipeptidyl peptidase-4 inhibitor. In this study, cytotoxic, genotoxic effects and DNA damage of SAX on human lymphocytes were investigated. For this purpose, Single Cell Gel Electrophoresis (SCGE), Micronucleus (MN) and Mitotic Index (MI) tests were used. Based on the daily doses of SAX, 0.017, 0.035, 0.07, 0.14 µg/mL concentrations used for the study. SAX significantly reduced the MI only at the highest concentration (0.14 µg/mL) for 24 hours, and 0.07- and 0.14-µg/mL concentrations for 48 hours. SAX did not cause a statistically significant change in MN frequency (except for concentration 0.14 µg/mL). In the SCGE test, a statistically significant increase of comet tail length was observed at 0.07- and 0.14-µg/mL concentrations. SAX did not cause a statistically significant change in comet tail moment and tail intensity (except for concentration 0.14 µg/mL). As a result, SAX caused statistically differences in the SCGE, MI and MN tests only at the highest concentrations that are not recommended commercial use (except for tail length, 0.035 µg/mL). When the results of all these studies are evaluated together, it can be said that SAX has no aneugenic, mutagenic and clastogenic effects at daily doses in in vitro studies on human lymphocytes.