Author:
Giordani Camila F. A.,Campanharo Sarah,Wingert Nathalie R.,Bueno Lívia M.,Manoel Joanna W.,Costa Barbara,Cattani Shanda,Arbo Marcelo Dutra,Garcia Solange Cristina,Garcia Cássia Virginia,Volpato Nádia Maria,Schapoval Elfrides Eva Scherman,Steppe Martin
Abstract
Abstract
Background
The presence of impurities in some drugs may compromise the safety and efficacy of the patient’s treatment. Therefore, establishing of the biological safety of the impurities is essential. Diabetic patients are predisposed to tissue damage due to an increased oxidative stress process; and drug impurities may contribute to these toxic effects. In this context, the aim of this work was to study the toxicity, in 3 T3 cells, of the antidiabetic agents sitagliptin, vildagliptin, and their two main impurities of synthesis (S1 and S2; V1 and V2, respectively).
Methods
MTT reduction and neutral red uptake assays were performed in cytotoxicity tests. In addition, DNA damage (measured by comet assay), intracellular free radicals (by DCF), NO production, and mitochondrial membrane potential (ΔψM) were evaluated.
Results
Cytotoxicity was observed for impurity V2. Free radicals generation was found at 1000 μM of sitagliptin and 10 μM of both vildagliptin impurities (V1 and V2). A decrease in NO production was observed for all vildagliptin concentrations. No alterations were observed in ΔψM or DNA damage at the tested concentrations.
Conclusions
This study demonstrated that the presence of impurities might increase the cytotoxicity and oxidative stress of the pharmaceutical formulations at the concentrations studied.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Pharmacology
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