Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHP |
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Authors: | Monia Lenzi,Veronica Cocchi,Sofia Gasperini,Raffaella Arf ,Matteo Marti,Patrizia Hrelia |
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Affiliation: | 1.Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy; (M.L.); (V.C.); (S.G.); (P.H.);2.Section of Legal Medicine and LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy;3.Collaborative Center for the Italian National Early Warning System, Department of Anti-Drug Policies, Presidency of the Council of Ministers, 44121 Ferrara, Italy |
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Abstract: | Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present work was to evaluate their mutagenicity on TK6 cells. On the basis of cytotoxicity and cytostasis results, we selected the concentrations (35–100 µM) to be used in the further analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by flow cytometry. Mexedrone demonstrated its mutagenic potential contrary to the other two compounds; we then proceeded by repeating the analyzes in the presence of extrinsic metabolic activation in order to check if it was possible to totally exclude the mutagenic capacity for α-PVP and α-PHP. The results demonstrated instead the mutagenicity of their metabolites. We then evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the highlighted effects but the results did not show a statistically significant increase in ROS levels for any of the tested substances. Anyway, our outcomes emphasize the importance of mutagenicity evaluation for a complete assessment of the risk associated with synthetic cathinones exposure. |
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Keywords: | synthetic cathinones, mexedrone, α -PVP, α -PHP, mutagenicity, S9 mix, ROS, flow cytometry, novel psychoactive substances |
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