Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHP

Mexedrone, alpha-PVP and alpha-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 mu M) 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 alpha-PVP and alpha-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.

Automated summary

The study evaluated the mutagenicity of Mexedrone, alpha-PVP and alpha-PHP on DNA, indicating Mexedrone's mutagenic potential while the other two compounds did not show mutagenicity; even with extrinsic metabolic activation, the mutagenic capacity of alpha-PVP and alpha-PHP could not be excluded, and their metabolites were found to be mutagenic. The induction of reactive oxygen species (ROS) was evaluated as a possible mechanism for the effects but did not show a statistically significant increase in ROS levels for any of the tested substances.