PMID- 30925718
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20221207
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 7
DP  - 2019 Mar 28
TI  - Molecular Toxicological Mechanisms of Synthetic Cathinones on C2C12 Myoblasts.
LID - 10.3390/ijms20071561 [doi]
LID - 1561
AB  - 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 (alpha-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 muM. The two pyrovalerone derivatives alpha-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.
FAU - Zhou, Xun
AU  - Zhou X
AD  - Division of Clinical Pharmacology & Toxicology, Department of Biomedicine, 
      University Hospital Basel and University of Basel, 4031 Basel, Switzerland. 
      Xun.Zhou@unibas.ch.
FAU - Luethi, Dino
AU  - Luethi D
AD  - Division of Clinical Pharmacology & Toxicology, Department of Biomedicine, 
      University Hospital Basel and University of Basel, 4031 Basel, Switzerland. 
      dino.luethi@unibas.ch.
FAU - Sanvee, Gerda M
AU  - Sanvee GM
AD  - Division of Clinical Pharmacology & Toxicology, Department of Biomedicine, 
      University Hospital Basel and University of Basel, 4031 Basel, Switzerland. 
      Gerda.Sanvee@unibas.ch.
FAU - Bouitbir, Jamal
AU  - Bouitbir J
AUID- ORCID: 0000-0003-4453-9457
AD  - Division of Clinical Pharmacology & Toxicology, Department of Biomedicine, 
      University Hospital Basel and University of Basel, 4031 Basel, Switzerland. 
      Jamal.Bouitbir@unibas.ch.
AD  - Swiss Centre for Applied Human Toxicology, 4031 Basel, Switzerland. 
      Jamal.Bouitbir@unibas.ch.
FAU - Liechti, Matthias E
AU  - Liechti ME
AUID- ORCID: 0000-0002-1765-9659
AD  - Division of Clinical Pharmacology & Toxicology, Department of Biomedicine, 
      University Hospital Basel and University of Basel, 4031 Basel, Switzerland. 
      Matthias.Liechti@unibas.ch.
AD  - Swiss Centre for Applied Human Toxicology, 4031 Basel, Switzerland. 
      Matthias.Liechti@unibas.ch.
FAU - Krahenbuhl, Stephan
AU  - Krahenbuhl S
AD  - Division of Clinical Pharmacology & Toxicology, Department of Biomedicine, 
      University Hospital Basel and University of Basel, 4031 Basel, Switzerland. 
      stephan.kraehenbuehl@usb.ch.
AD  - Swiss Centre for Applied Human Toxicology, 4031 Basel, Switzerland. 
      stephan.kraehenbuehl@usb.ch.
LA  - eng
GR  - SNF 31003A_156270/Schweizerischer Nationalfonds zur Forderung der 
      Wissenschaftlichen Forschung/
PT  - Journal Article
DEP - 20190328
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one)
RN  - 0 (Benzodioxoles)
RN  - 0 (Pentanones)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (Pyrrolidines)
RN  - 0 (alpha-pyrrolidinovalerophenone)
RN  - 11062-77-4 (Superoxides)
RN  - 44RAL3456C (Methamphetamine)
RN  - 8BA8T27317 (mephedrone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - L4I4B1R01F (methylone)
RN  - 0 (Synthetic Cathinone)
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Benzodioxoles/*toxicity
MH  - Cell Line
MH  - Methamphetamine/*analogs & derivatives/toxicity
MH  - Mice
MH  - Mitochondria/drug effects/metabolism/pathology
MH  - Myoblasts/*drug effects/metabolism/pathology
MH  - Oxygen Consumption/drug effects
MH  - Pentanones/*toxicity
MH  - Psychotropic Drugs/*toxicity
MH  - Pyrrolidines/*toxicity
MH  - Superoxides/metabolism
MH  - Synthetic Cathinone
PMC - PMC6479684
OTO - NOTNLM
OT  - electron transport chain
OT  - mitochondria
OT  - skeletal muscle toxicity
OT  - synthetic cathinones
COIS- The authors declare no conflict of interest.
EDAT- 2019/03/31 06:00
MHDA- 2019/07/30 06:00
PMCR- 2019/04/01
CRDT- 2019/03/31 06:00
PHST- 2019/01/31 00:00 [received]
PHST- 2019/03/22 00:00 [revised]
PHST- 2019/03/22 00:00 [accepted]
PHST- 2019/03/31 06:00 [entrez]
PHST- 2019/03/31 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2019/04/01 00:00 [pmc-release]
AID - ijms20071561 [pii]
AID - ijms-20-01561 [pii]
AID - 10.3390/ijms20071561 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Mar 28;20(7):1561. doi: 10.3390/ijms20071561.