3,4-methylenedioxypyrovalerone (MDPV) Induces Cytotoxic Effects on Human Dopaminergic SH-SY5Y Cells
Author(s): Hector Rosas-Hernandez, Elvis Cuevas, Susan M Lantz, Syed Z Imam, Kenner C Rice, Brenda M Gannon, William E Fantegrossi, Merle G Paule, and Syed F Ali
Abstract
Background. Synthetic cathinones are a rapidly growing group of psychostimulant drugs usually referred to as “bath salts” and have been used as an alternative to classic amphetamine-like drugs, with 3,4-methylenedioxypyrovalerone (MDPV) being one of the most prevalent constituents. Consistent with the effects of other psychostimulants, MDPV may induce neurotoxicity by altering monoamine systems in the brain or by inducing neuronal apoptosis. Purpose. The aim of this study was to evaluate the effects of MDPV on the human dopaminergic cell line SH-SY5Y. Experimental design. After 24-hour exposure to MDPV (100 μM to 2.5mM), cytotoxicity, cellular proliferation, and apoptosis were evaluated, whereas reactive oxygen species (ROS) production was evaluated at 2 h, 4 h, 6 h, 22 h, and 24 h. Results. MDPV increased ROS production after 1 h, 4 h, and 6 h of exposure in all but the highest concentration; a moderate increase was observed at 22 h and 24 h. Only high concentrations of the drug decreased cellular proliferation and induced apoptosis and necrosis. Conclusion. MDPV induces dopaminergic toxicity by decreasing cellular proliferation and by increasing apoptosis and necrosis. The production of ROS may play a role in the early response to the drug.
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