PMID- 28067045
OWN - NLM
STAT- MEDLINE
DCOM- 20170502
LR  - 20221207
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Linking)
VI  - 8
IP  - 4
DP  - 2017 Apr 19
TI  - Neurotoxicity of beta-Keto Amphetamines: Deathly Mechanisms Elicited by Methylone 
      and MDPV in Human Dopaminergic SH-SY5Y Cells.
PG  - 850-859
LID - 10.1021/acschemneuro.6b00421 [doi]
AB  - Synthetic cathinones (beta-keto amphetamines) act as potent CNS stimulants similarly 
      to classical amphetamines, which raise concerns about their potential neurotoxic 
      effects. The present in vitro study aimed to explore and compare the mechanisms 
      underlying the neurotoxicity of two commonly abused cathinone derivatives, 
      3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone 
      (MDPV), with those of 3,4-methylenedioxymethamphetamine (MDMA), using 
      undifferentiated and differentiated SH-SY5Y cells. Following a 24 h exposure 
      period, methylone and MDPV induced loss of cell viability in a 
      concentration-dependent manner, in the following order of potency: MDPV  approximately  MDMA > 
      methylone. Dopaminergic differentiated cells evidenced higher sensitivity to the 
      neurotoxic effects of both cathinones and MDMA than the undifferentiated ones, 
      but this effect was not inhibited by the DAT inhibitor GBR 12909. Intracellular 
      oxidative stress mediated by methylone and MDPV was demonstrated by the increase 
      in reactive oxygen and nitrogen species (ROS and RNS) production, depletion of 
      intracellular reduced glutathione and increased oxidized glutathione levels. All 
      three drugs elicited mitochondrial impairment, characterized by the mitochondrial 
      membrane potential (Deltapsim) dissipation and intracellular ATP depletion. Apoptosis 
      was found to be a common mechanism of cell death induced by methylone and MDPV, 
      with evident chromatin condensation and formation of pyknotic nuclei, and 
      activation of caspases 3, 8, and 9. In conclusion, the present data shows that 
      oxidative stress and mitochondrial dysfunction play a role in cathinones-induced 
      neuronal damage, ultimately leading to cell death by apoptosis.
FAU - Valente, Maria Joao
AU  - Valente MJ
AD  - UCIBIO-REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of 
      Porto , 4050-313 Porto, Portugal.
FAU - Bastos, Maria de Lourdes
AU  - Bastos ML
AD  - UCIBIO-REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of 
      Porto , 4050-313 Porto, Portugal.
FAU - Fernandes, Eduarda
AU  - Fernandes E
AD  - UCIBIO-REQUIMTE, Laboratory of Applied Chemistry, Faculty of Pharmacy, University 
      of Porto , 4050-313 Porto, Portugal.
FAU - Carvalho, Felix
AU  - Carvalho F
AD  - UCIBIO-REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of 
      Porto , 4050-313 Porto, Portugal.
FAU - Guedes de Pinho, Paula
AU  - Guedes de Pinho P
AD  - UCIBIO-REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of 
      Porto , 4050-313 Porto, Portugal.
FAU - Carvalho, Marcia
AU  - Carvalho M
AUID- ORCID: 0000-0001-9884-4751
AD  - UCIBIO-REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of 
      Porto , 4050-313 Porto, Portugal.
AD  - FP-ENAS, CEBIMED, Fundacao Ensino e Cultura Fernando Pessoa , 4249-004 Porto, 
      Portugal.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170126
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
RN  - 0 (Benzodioxoles)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Pyrrolidines)
RN  - 44RAL3456C (Methamphetamine)
RN  - L4I4B1R01F (methylone)
RN  - 0 (Synthetic Cathinone)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Benzodioxoles/*toxicity
MH  - Cell Survival/drug effects
MH  - Central Nervous System Stimulants/*toxicity
MH  - Dopaminergic Neurons/*drug effects
MH  - Humans
MH  - Methamphetamine/*analogs & derivatives/toxicity
MH  - Oxidative Stress/drug effects
MH  - Pyrrolidines/*toxicity
MH  - Synthetic Cathinone
OTO - NOTNLM
OT  - apoptosis
OT  - mitochondrial impairment
OT  - neurotoxicity
OT  - oxidative stress
OT  - synthetic cathinones
OT  - beta-Keto amphetamines
EDAT- 2017/01/10 06:00
MHDA- 2017/05/04 06:00
CRDT- 2017/01/10 06:00
PHST- 2017/01/10 06:00 [pubmed]
PHST- 2017/05/04 06:00 [medline]
PHST- 2017/01/10 06:00 [entrez]
AID - 10.1021/acschemneuro.6b00421 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2017 Apr 19;8(4):850-859. doi: 10.1021/acschemneuro.6b00421. 
      Epub 2017 Jan 26.