In vitro evaluation of mutagenicity and genotoxicity of sitagliptin alone and in combination with artificial sweeteners
Purpose: To determine the in vitro genotoxicity and mutagenicity of sitagliptin alone and in combination with three commonly used artificial sweeteners (saccharin, aspartame and acesulfame-k).
Methods: The in vitro genotoxicity and mutagenicity of Sitagliptin alone and in combination with three popular artificial sweeteners (saccharin, aspartame and acesulfame-k) were evaluated by Comet and Ames assays, respectively.
Results: Sitagliptin demonstrated mutagenic potential only to TA 98 with S9 mix at a concentration of 3040 μg/plate. The mutagenicity of sitagliptin was enhanced when tested in combination with the artificial sweeteners. Furthermore, sitagliptin also caused pronounced DNA fragmentation at higher doses compared with negative control.
Conclusion: At higher doses, sitagliptin showed both mutagenicity and genotoxicity. Thus, long-term use of artificial sweeteners with sitagliptin may lead to increase in both mutagenicity and genotoxicity.
Keywords: Sitagliptin, Artificial sweeteners, Comet assay, DNA damage, Ames assay, Genotoxicity, Mutagenicity
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