Possible genotoxic effects of dapagliflozin using SMART and comet tests, and behavioral toxicity in <i>Drosophila melanogaster</i>

Dapagliflozin (DAPA) is a sodium-glucose cotransporter (SGLT) inhibitor used in the treatment of type 2 diabetes mellitus. DAPA, used in the treatment of type 2 diabetes mellitus (T2DM), has been shown to cause liver damage in clinical studies, and has raised concerns due to drug-related breast and bladder cancer cases. However, due to the lack of information regarding its potential effects on humans, genotoxicity assessments of DAPA are necessary, and its use should be reconsidered following these assessments. For all these reasons, this study aimed to determine the possible cytotoxic and genotoxic effects of DAPA on <i>Drosophila melanogaster</i>. Four DAPA concentrations (0.1, 1, 5, and 10 mM) were assessed for behavioral toxicity and DNA damage detection using the Comet assay. Furthermore, the genotoxic potential of three DAPA concentrations (0.225, 0.45, and 0.9 mM) was assessed using the Drosophila SMART assay. According to the results of behavioral toxicity experiments, changes in larval weight, larval crawling, negative geotaxis, and adult individual formation success at specific doses were found to be statistically significant. However, changes in pupal formation success, pupal position, and adult individual weight were not found to be statistically significant. In the Comet test results, changes were found in all treatment groups compared to the control group, while in the SMART test, only the frequency increases in the 0.9 mM treatment group were found to be statistically significant. Molecular techniques are needed to explain the exact mechanism of the changes observed in the test systems.