We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
In vitro toxic evaluation of two gliptins and their main impurities of synthesis.
- Authors
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
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.
- Subjects
DNA; DNA damage; OXIDATIVE stress; FREE radicals; PATIENT safety; MITOCHONDRIAL membranes
- Publication
BMC Pharmacology & Toxicology, 2019, Vol 20, p1
- ISSN
2050-6511
- Publication type
Article
- DOI
10.1186/s40360-019-0354-2