PMID- 26509576
OWN - NLM
STAT- MEDLINE
DCOM- 20160616
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 10
DP  - 2015
TI  - Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing 
      Cellular Stress.
PG  - e0141502
LID - 10.1371/journal.pone.0141502 [doi]
LID - e0141502
AB  - Binge drinking is a common pattern of ethanol consumption among young people. 
      Binge drinkers are especially susceptible to brain damage when other substances 
      are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The 
      aim of the present work was to study the mechanisms implicated in the adaptive 
      changes observed after administration of these drugs of abuse. So, we have 
      evaluated the cardiac sympathetic activity and the expression and activation of 
      heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone 
      and in combination with MDMA. Both parameters are markers of stressful situations 
      and they could be modified inducing several alterations in different systems. 
      Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in 
      the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) 
      turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 
      expression and its phosphorylation at serine 82 were evaluated in adolescent mice 
      48 h, 72 h, and 7 days after treatments in the left ventricle. NA and 
      normetanephrine (NMN) were determined by high-performance liquid chromatography 
      (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative 
      blot immunollabeling using specific antibodies. Ethanol and MDMA 
      co-administration increased NA turnover and TH expression and phosphorylation 
      versus the consumption of each one of these drugs. In parallel with the described 
      modifications in the cardiac sympathetic activity, our results showed that binge 
      ethanol+MDMA exposure is associated with an increase in HSP27 expression and 
      phosphorylation in the left ventricle, supporting the idea that the combination 
      of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone.
FAU - Navarro-Zaragoza, Javier
AU  - Navarro-Zaragoza J
AD  - Department of Pharmacology, Faculty of Medicine, University of Murcia, Murcia, 
      Spain.
FAU - Ros-Simo, Clara
AU  - Ros-Simo C
AD  - Grup de Recerca en Neurobiologia del Comportament (GRNC), Universitat Pompeu 
      Fabra, Barcelona, Spain.
FAU - Milanes, Maria-Victoria
AU  - Milanes MV
AD  - Department of Pharmacology, Faculty of Medicine, University of Murcia, Murcia, 
      Spain.
FAU - Valverde, Olga
AU  - Valverde O
AD  - Grup de Recerca en Neurobiologia del Comportament (GRNC), Universitat Pompeu 
      Fabra, Barcelona, Spain.
FAU - Laorden, Maria-Luisa
AU  - Laorden ML
AD  - Department of Pharmacology, Faculty of Medicine, University of Murcia, Murcia, 
      Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151028
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HSP27 Heat-Shock Proteins)
RN  - 0J45DE6B88 (Normetanephrine)
RN  - 3K9958V90M (Ethanol)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
EIN - PLoS One. 2015;10(11):e0143462. PMID: 26569398
MH  - Animals
MH  - *Binge Drinking
MH  - Cardiotoxicity
MH  - Ethanol/*toxicity
MH  - HSP27 Heat-Shock Proteins/metabolism
MH  - Heart/*drug effects
MH  - Heart Ventricles/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Models, Animal
MH  - Myocardium/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Norepinephrine/metabolism
MH  - Normetanephrine/metabolism
MH  - Phosphorylation
MH  - Stress, Physiological/*drug effects
MH  - Tyrosine 3-Monooxygenase/metabolism
PMC - PMC4624901
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/10/29 06:00
MHDA- 2016/06/17 06:00
PMCR- 2015/10/28
CRDT- 2015/10/29 06:00
PHST- 2015/08/13 00:00 [received]
PHST- 2015/10/08 00:00 [accepted]
PHST- 2015/10/29 06:00 [entrez]
PHST- 2015/10/29 06:00 [pubmed]
PHST- 2016/06/17 06:00 [medline]
PHST- 2015/10/28 00:00 [pmc-release]
AID - PONE-D-15-33069 [pii]
AID - 10.1371/journal.pone.0141502 [doi]
PST - epublish
SO  - PLoS One. 2015 Oct 28;10(10):e0141502. doi: 10.1371/journal.pone.0141502. 
      eCollection 2015.