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Open AccessArticle

Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction

1
Centre for Forensic Science, School of Mathematical and Physical Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia
2
Discipline of Pathology, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1370; https://doi.org/10.3390/ijms21041370
Received: 31 December 2019 / Revised: 13 February 2020 / Accepted: 16 February 2020 / Published: 18 February 2020
(This article belongs to the Section Biochemistry)
Increasing reports of neurological and psychiatric complications due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the precise mechanism of SC toxicity is unclear. This paucity of understanding highlights the need to investigate the in-vitro toxicity and mechanistic pathways of three SCs: butylone, pentylone, and 3,4-Methylenedioxypyrovalerone (MDPV). Human neuronal cells of SH-SY5Y were cultured in supplemented DMEM/F12 media and differentiated to a neuronal phenotype using retinoic acid (10 μM) and 12-O-tetradecanoylphorbol-13-acetate (81 nM). Trypan blue and lactate dehydrogenase assays were utilized to assess the neurotoxicity potential and potency of these three SCs. To investigate the underlying neurotoxicity mechanisms, measurements included markers of oxidative stress, mitochondrial bioenergetics, and intracellular calcium (Ca2+), and cell death pathways were evaluated at two doses (EC15 and EC40), for each drug tested. Following 24 h of treatment, all three SCs exhibited a dose-dependent neurotoxicity, characterized by a significant (p < 0.0001 vs. control) production of reactive oxygen species, decreased mitochondrial bioenergetics, and increased intracellular Ca2+ concentrations. The activation of caspases 3 and 7 implicated the orchestration of mitochondrial-mediated neurotoxicity mechanisms for these SCs. Identifying novel therapeutic agents to enhance an altered mitochondrial function may help in the treatment of acute-neurological complications arising from the illicit use of these SCs. View Full-Text
Keywords: mitochondrial dysfunction; calcium dysregulation; apoptosis; synthetic cathinones; SH-SY5Y mitochondrial dysfunction; calcium dysregulation; apoptosis; synthetic cathinones; SH-SY5Y
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MDPI and ACS Style

Leong, H.S.; Philp, M.; Simone, M.; Witting, P.K.; Fu, S. Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction. Int. J. Mol. Sci. 2020, 21, 1370. https://doi.org/10.3390/ijms21041370

AMA Style

Leong HS, Philp M, Simone M, Witting PK, Fu S. Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction. International Journal of Molecular Sciences. 2020; 21(4):1370. https://doi.org/10.3390/ijms21041370

Chicago/Turabian Style

Leong, Huey S.; Philp, Morgan; Simone, Martin; Witting, Paul K.; Fu, Shanlin. 2020. "Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction" Int. J. Mol. Sci. 21, no. 4: 1370. https://doi.org/10.3390/ijms21041370

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