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Hyperthermia Increases Neurotoxicity Associated with Novel Methcathinones

Division of Clinical Pharmacology & Toxicology, University Hospital Basel, 4031 Basel, Switzerland
Department of Biomedicine, University of Basel, 4031 Basel, Switzerland
Swiss Centre for Applied Human Toxicology, 4031 Basel, Switzerland
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 965;
Received: 24 February 2020 / Revised: 29 March 2020 / Accepted: 9 April 2020 / Published: 14 April 2020
(This article belongs to the Section Autophagy)
Hyperthermia is one of the severe acute adverse effects that can be caused by the ingestion of recreational drugs, such as methcathinones. The effect of hyperthermia on neurotoxicity is currently not known. The primary aim of our study was therefore to investigate the effects of hyperthermia (40.5 °C) on the neurotoxicity of methcathinone (MC), 4-chloromethcathinone (4-CMC), and 4-methylmethcathinone (4-MMC) in SH-SY5Y cells. We found that 4-CMC and 4-MMC were cytotoxic (decrease in cellular ATP and plasma membrane damage) under both hyper- (40.5 °C) and normothermic conditions (37 °C), whereby cells were more sensitive to the toxicants at 40.5 °C. 4-CMC and 4-MMC impaired the function of the mitochondrial electron transport chain and increased mitochondrial formation of reactive oxygen species (ROS) in SH-SY5Y cells, which were accentuated under hyperthermic conditions. Hyperthermia was associated with a rapid expression of the 70 kilodalton heat shock protein (Hsp70), which partially prevented cell death after 6 h of exposure to the toxicants. After 24 h of exposure, autophagy was stimulated by the toxicants and by hyperthermia but could only partially prevent cell death. In conclusion, hyperthermic conditions increased the neurotoxic properties of methcathinones despite the stimulation of protective mechanisms. These findings may be important for the understanding of the mechanisms and clinical consequences of the neurotoxicity associated with these compounds. View Full-Text
Keywords: autophagy; hyperthermia; methcathinone; mitochondria; neurotoxicity autophagy; hyperthermia; methcathinone; mitochondria; neurotoxicity
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MDPI and ACS Style

Zhou, X.; Bouitbir, J.; Liechti, M.E.; Krähenbühl, S.; Mancuso, R.V. Hyperthermia Increases Neurotoxicity Associated with Novel Methcathinones. Cells 2020, 9, 965.

AMA Style

Zhou X, Bouitbir J, Liechti ME, Krähenbühl S, Mancuso RV. Hyperthermia Increases Neurotoxicity Associated with Novel Methcathinones. Cells. 2020; 9(4):965.

Chicago/Turabian Style

Zhou, Xun, Jamal Bouitbir, Matthias E. Liechti, Stephan Krähenbühl, and Riccardo V. Mancuso 2020. "Hyperthermia Increases Neurotoxicity Associated with Novel Methcathinones" Cells 9, no. 4: 965.

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