Cytotoxic Effects of 3,4-Catechol-PV (One Major MDPV Metabolite) on Human Dopaminergic SH-SY5Y Cells

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Abstract

3,4-Methylenedioxypyrovalerone (MDPV), one of the most commonly abused synthetic cathinones, has caused several intoxications and deaths despite its short presence on the market. Apart from its effects on the monoamine systems in the brain, recent in vitro investigations have revealed cytotoxicity. In this study, the effects of increasing concentrations (10-1000 μM) of 3,4-Catechol-PV, one of major MDPV metabolites, on cell viability, morphology, and apoptosis have been evaluated after acute exposure (24-48 h) in human neuroblastoma SH-SY5Y cells-undifferentiated and differentiated to a more mature neuronal-like phenotype. Results indicated the following: (i) Cell viability: concentration-dependent decrease (15-55%) in differentiated SH-SY5Y after 24 h, with no exacerbation after 48 h (LC50 values 1028 and 951 μM, respectively); marked concentration-dependent decrease after 48 h (20-63%) in undifferentiated SH-SY5Y (LC50 553.9 μM) with mild effect (18-22% cell death) after 24 h at ≥ 500 μM only; the lowest toxic concentrations were 500 and 100 μM after 24 h, for undifferentiated and differentiated SH-SY5Y, respectively, and 10 μM after 48 h. (ii) Concentration- and time-dependent alterations of cell morphology in both SH-SY5Y types characterized by several intracellular cytoplasmic vesicles (undifferentiated more susceptible (effect at ≥ 50 μM) than differentiated cells (effect at ≥ 100 μM)), loss of the typical cell shape, neurite retraction, and cell density decrease. (iii) Activation of caspase-3 enzyme in differentiated and undifferentiated cells after 48 h. These findings suggest the potential involvement of 3,4-Catechol-PV in MDPV-induced neurotoxicity and support the use of this human cellular model as a species-specific in vitro tool to clarify the neurotoxicity mechanisms of synthetic cathinones and metabolites.

Original languageEnglish
Pages (from-to)49-62
Number of pages14
JournalNeurotoxicity Research
Volume35
Issue number1
DOIs
Publication statusPublished - Jan 2019

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Keywords

  • Antineoplastic Agents/pharmacology
  • Benzodioxoles/pharmacology
  • Caspase 3/metabolism
  • Cell Differentiation/drug effects
  • Cell Line, Tumor
  • Cell Size/drug effects
  • Dopamine/metabolism
  • Dopamine Uptake Inhibitors/pharmacology
  • Dopamine beta-Hydroxylase/metabolism
  • Dopaminergic Neurons/drug effects
  • Dose-Response Relationship, Drug
  • Guaiacol/analogs & derivatives
  • Humans
  • Mitochondria/drug effects
  • Nerve Tissue Proteins/metabolism
  • Neuroblastoma/pathology
  • Pyrrolidines/pharmacology
  • Statistics, Nonparametric
  • Time Factors
  • Tretinoin/pharmacology
  • Tyrosine 3-Monooxygenase/metabolism

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