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Open AccessArticle

Molecular Toxicological Mechanisms of Synthetic Cathinones on C2C12 Myoblasts

1
Division of Clinical Pharmacology & Toxicology, Department of Biomedicine, University Hospital Basel and University of Basel, 4031 Basel, Switzerland
2
Swiss Centre for Applied Human Toxicology, 4031 Basel, Switzerland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1561; https://doi.org/10.3390/ijms20071561
Received: 31 January 2019 / Revised: 22 March 2019 / Accepted: 22 March 2019 / Published: 28 March 2019
(This article belongs to the Special Issue Cell Targets and Toxicity)
Synthetic cathinones are popular psychoactive substances that may cause skeletal muscle damage. In addition to indirect sympathomimetic myotoxicity, these substances could be directly myotoxic. Since studies in myocytes are currently lacking, the aim of the present study was to investigate potential toxicological effects by synthetic cathinones on C2C12 myoblasts (mouse skeletal muscle cell line). We exposed C2C12 myoblasts to 3-methylmethcathinone, 4-methylmethcathinone (mephedrone), 3,4-methylenedioxymethcathinone (methylone), 3,4-methylenedioxypyrovalerone (MDPV), alpha-pyrrolidinovalerophenone (α-PVP), and naphthylpyrovalerone (naphyrone) for 1 or 24 h before cell membrane integrity, ATP content, mitochondrial oxygen consumption, and mitochondrial superoxide production was measured. 3,4-Methylenedioxymethamphetamine (MDMA) was included as a reference compound. All investigated synthetic cathinones, as well as MDMA, impaired cell membrane integrity, depleted ATP levels, and increased mitochondrial superoxide concentrations in a concentration-dependent manner in the range of 50–2000 μM. The two pyrovalerone derivatives α-PVP and naphyrone, and MDMA, additionally impaired basal and maximal cellular respiration, suggesting mitochondrial dysfunction. Alpha-PVP inhibited complex I, naphyrone complex II, and MDMA complex I and III, whereas complex IV was not affected. We conclude that, in addition to sympathetic nervous system effects and strenuous muscle exercise, direct effects of some cathinones on skeletal muscle mitochondria may contribute to myotoxicity in susceptible synthetic cathinone drugs users. View Full-Text
Keywords: synthetic cathinones; skeletal muscle toxicity; mitochondria; electron transport chain synthetic cathinones; skeletal muscle toxicity; mitochondria; electron transport chain
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MDPI and ACS Style

Zhou, X.; Luethi, D.; Sanvee, G.M.; Bouitbir, J.; Liechti, M.E.; Krähenbühl, S. Molecular Toxicological Mechanisms of Synthetic Cathinones on C2C12 Myoblasts. Int. J. Mol. Sci. 2019, 20, 1561. https://doi.org/10.3390/ijms20071561

AMA Style

Zhou X, Luethi D, Sanvee GM, Bouitbir J, Liechti ME, Krähenbühl S. Molecular Toxicological Mechanisms of Synthetic Cathinones on C2C12 Myoblasts. International Journal of Molecular Sciences. 2019; 20(7):1561. https://doi.org/10.3390/ijms20071561

Chicago/Turabian Style

Zhou, Xun; Luethi, Dino; Sanvee, Gerda M.; Bouitbir, Jamal; Liechti, Matthias E.; Krähenbühl, Stephan. 2019. "Molecular Toxicological Mechanisms of Synthetic Cathinones on C2C12 Myoblasts" Int. J. Mol. Sci. 20, no. 7: 1561. https://doi.org/10.3390/ijms20071561

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