PMID- 27320055
OWN - NLM
STAT- MEDLINE
DCOM- 20170726
LR  - 20221207
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 629
DP  - 2016 Aug 26
TI  - Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 
      3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in 
      bovine brain microvessel endothelial cells.
PG  - 125-130
LID - S0304-3940(16)30438-4 [pii]
LID - 10.1016/j.neulet.2016.06.029 [doi]
AB  - Designer drugs such as synthetic psychostimulants are indicative of a worldwide 
      problem of drug abuse and addiction. In addition to methamphetamine (METH), these 
      drugs include 3,4-methylenedioxy-methamphetamine (MDMA) and commercial 
      preparations of synthetic cathinones including 3,4-methylenedioxypyrovalerone 
      (MDPV), typically referred to as "bath salts." These psychostimulants exert 
      neurotoxic effects by altering monoamine systems in the brain. Additionally, METH 
      and MDMA adversely affect the integrity of the blood-brain barrier (BBB): there 
      are no current reports on the effects of MDPV on the BBB. The aim of this study 
      was to compare the effects of METH, MDMA and MDPV on bovine brain microvessel 
      endothelial cells (bBMVECs), an accepted in vitro model of the BBB. Confluent 
      bBMVEC monolayers were treated with METH, MDMA and MDPV (0.5mM-2.5mM) for 24h. 
      METH and MDMA increased lactate dehydrogenase release only at the highest 
      concentration (2.5mM), whereas MDPV induced cytotoxicity at all concentrations. 
      MDMA and METH decreased cellular proliferation only at 2.5mM, with similar 
      effects observed after MDPV exposures starting at 1mM. Only MDPV increased 
      reactive oxygen species production at all concentrations tested whereas all 3 
      drugs increased nitric oxide production. Morphological analysis revealed 
      different patterns of compound-induced cell damage. METH induced vacuole 
      formation at 1mM and disruption of the monolayer at 2.5mM. MDMA induced 
      disruption of the endothelial monolayer from 1mM without vacuolization. On the 
      other hand, MDPV induced monolayer disruption at doses >/=0.5mM without vacuole 
      formation; at 2.5mM, the few remaining cells lacked endothelial morphology. These 
      data suggest that even though these synthetic psychostimulants alter 
      monoaminergic systems, they each induce BBB toxicity by different mechanisms with 
      MDPV being the most toxic.
CI  - Published by Elsevier Ireland Ltd.
FAU - Rosas-Hernandez, Hector
AU  - Rosas-Hernandez H
AD  - Neurochemistry Laboratory, Division of Neurotoxicology, National Center for 
      Toxicological Research/FDA, Jefferson, AR, USA.
FAU - Cuevas, Elvis
AU  - Cuevas E
AD  - Neurochemistry Laboratory, Division of Neurotoxicology, National Center for 
      Toxicological Research/FDA, Jefferson, AR, USA.
FAU - Lantz, Susan M
AU  - Lantz SM
AD  - Neurochemistry Laboratory, Division of Neurotoxicology, National Center for 
      Toxicological Research/FDA, Jefferson, AR, USA.
FAU - Rice, Kenner C
AU  - Rice KC
AD  - Drug Design and Synthesis Section, Molecular Targets and Medications Discovery 
      Branch, NIDA/NIAAA, Bethesda, MD, USA.
FAU - Gannon, Brenda M
AU  - Gannon BM
AD  - Department of Pharmacology & Toxicology, UAMS, Little Rock, AR, USA.
FAU - Fantegrossi, William E
AU  - Fantegrossi WE
AD  - Department of Pharmacology & Toxicology, UAMS, Little Rock, AR, USA.
FAU - Gonzalez, Carmen
AU  - Gonzalez C
AD  - Facultad de Ciencias Quimicas, UASLP, SLP, Mexico.
FAU - Paule, Merle G
AU  - Paule MG
AD  - Neurochemistry Laboratory, Division of Neurotoxicology, National Center for 
      Toxicological Research/FDA, Jefferson, AR, USA.
FAU - Ali, Syed F
AU  - Ali SF
AD  - Neurochemistry Laboratory, Division of Neurotoxicology, National Center for 
      Toxicological Research/FDA, Jefferson, AR, USA. Electronic address: 
      Syed.Ali@fda.hhs.gov.
LA  - eng
GR  - Z01 DA000532-01/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20160616
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Benzodioxoles)
RN  - 0 (Designer Drugs)
RN  - 0 (Dopamine Agents)
RN  - 0 (Pyrrolidines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Serotonin Agents)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 44RAL3456C (Methamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - 0 (Synthetic Cathinone)
SB  - IM
MH  - Animals
MH  - Benzodioxoles/*toxicity
MH  - Blood-Brain Barrier/*drug effects
MH  - Cattle
MH  - Cell Proliferation/drug effects
MH  - Designer Drugs/*toxicity
MH  - Dopamine Agents/administration & dosage
MH  - Endothelial Cells/*drug effects/metabolism/pathology
MH  - Methamphetamine/*toxicity
MH  - Microvessels/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Necrosis/chemically induced
MH  - Nitric Oxide/metabolism
MH  - Pyrrolidines/*toxicity
MH  - Reactive Oxygen Species/metabolism
MH  - Serotonin Agents/administration & dosage
MH  - Synthetic Cathinone
PMC - PMC4983252
MID - NIHMS806125
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - Cytotoxicity
OT  - MDMA
OT  - MDPV
OT  - Methamphetamine
EDAT- 2016/06/21 06:00
MHDA- 2017/07/27 06:00
PMCR- 2017/08/26
CRDT- 2016/06/21 06:00
PHST- 2016/04/29 00:00 [received]
PHST- 2016/06/07 00:00 [revised]
PHST- 2016/06/15 00:00 [accepted]
PHST- 2016/06/21 06:00 [entrez]
PHST- 2016/06/21 06:00 [pubmed]
PHST- 2017/07/27 06:00 [medline]
PHST- 2017/08/26 00:00 [pmc-release]
AID - S0304-3940(16)30438-4 [pii]
AID - 10.1016/j.neulet.2016.06.029 [doi]
PST - ppublish
SO  - Neurosci Lett. 2016 Aug 26;629:125-130. doi: 10.1016/j.neulet.2016.06.029. Epub 
      2016 Jun 16.