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

Autor: Teresa Coccini, Uliana De Simone, Marta Crevani, Sarah Vecchio
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Programmed cell death
Pyrrolidines
Time Factors
SH-SY5Y
Tyrosine 3-Monooxygenase
Dopamine
Cellular differentiation
Undifferentiated SH-SY5Y
Antineoplastic Agents
Nerve Tissue Proteins
Tretinoin
Dopamine beta-Hydroxylase
Pharmacology
Toxicology
Cell morphology
Statistics
Nonparametric

Neuroblastoma
03 medical and health sciences
0302 clinical medicine
Dopamine Uptake Inhibitors
Novel psychoactive substances
Cell Line
Tumor

medicine
Humans
Benzodioxoles
Viability assay
Synthetic cathinones
Cell Size
Dose-Response Relationship
Drug

Caspase 3
Chemistry
Differentiated SH-SY5Y
Dopaminergic Neurons
General Neuroscience
Guaiacol
Neurotoxicity
Cell Differentiation
Synthetic Cathinone
medicine.disease
Mitochondria
030104 developmental biology
Apoptosis
CNS
3
4-Methylenedioxypyrovalerone

030217 neurology & neurosurgery
Intracellular
DOI: 10.5281/zenodo.4066770
Popis: 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.
Databáze: OpenAIRE