PMID- 18761051
OWN - NLM
STAT- MEDLINE
DCOM- 20090105
LR  - 20161124
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 252
IP  - 1-3
DP  - 2008 Oct 30
TI  - Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes 
      liver to severe MDMA-induced toxicity in CD1 mice.
PG  - 64-71
LID - 10.1016/j.tox.2008.07.064 [doi]
AB  - 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is an amphetamine derivative 
      drug with entactogenic, empathogenic and hallucinogenic properties, commonly 
      consumed at rave parties in a polydrug abuse pattern, especially with cannabis, 
      tobacco and ethanol. Since both MDMA and ethanol may cause deleterious effects to 
      the liver, the evaluation of their putative hepatotoxic interaction is of great 
      interest, especially considering that most of the MDMA users are regular ethanol 
      consumers. Thus, the aim of the present study was to evaluate, in vivo, the acute 
      hepatotoxic effects of MDMA (10mg/kg i.p.) in CD-1 mice previously exposed to 12% 
      ethanol as drinking fluid (for 8 weeks). Body temperature was continuously 
      measured for 12h after MDMA administration and, after 24h, hepatic damage was 
      evaluated. The administration of MDMA to non pre-treated mice resulted in 
      sustained hyperthermia, which was significantly increased in ethanol pre-exposed 
      mice. A correspondent higher increase of hepatic heat shock transcription factor 
      (HSF-1) activation was also observed in the latter group. Furthermore, MDMA 
      administration resulted in liver damage as confirmed by histological analysis, 
      slight decrease in liver weight and increased plasma transaminases levels. These 
      hepatotoxic effects were also exacerbated when mice were pre-treated with 
      ethanol. The activities of some antioxidant enzymes (such as SOD, GPx and 
      Catalase) were modified by ethanol, MDMA and their joint action. The 
      hepatotoxicity resulting from the simultaneous exposure to MDMA and ethanol was 
      associated with a higher activation of NF-kappaB, indicating a pro-inflammatory 
      effect in this organ. In conclusion, the obtained results strongly suggest that 
      the consumption of ethanol increases the hyperthermic and hepatotoxic effects 
      associated with MDMA abuse.
FAU - Pontes, Helena
AU  - Pontes H
AD  - REQUIMTE, Toxicology Department, Faculty of Pharmacy, University of Porto, Rua 
      Anibal Cunha 164, 4099-030 Porto, Portugal. hpontes@ff.up.pt
FAU - Duarte, Jose Alberto
AU  - Duarte JA
FAU - de Pinho, Paula Guedes
AU  - de Pinho PG
FAU - Soares, Maria Elisa
AU  - Soares ME
FAU - Fernandes, Eduarda
AU  - Fernandes E
FAU - Dinis-Oliveira, Ricardo Jorge
AU  - Dinis-Oliveira RJ
FAU - Sousa, Carla
AU  - Sousa C
FAU - Silva, Renata
AU  - Silva R
FAU - Carmo, Helena
AU  - Carmo H
FAU - Casal, Susana
AU  - Casal S
FAU - Remiao, Fernando
AU  - Remiao F
FAU - Carvalho, Felix
AU  - Carvalho F
FAU - Bastos, Maria Lourdes
AU  - Bastos ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080807
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Antioxidants)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Hallucinogens)
RN  - 0 (NF-kappa B)
RN  - 3K9958V90M (Ethanol)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - GAN16C9B8O (Glutathione)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Aspartate Aminotransferases/blood
MH  - Body Temperature/drug effects
MH  - Central Nervous System Depressants/*toxicity
MH  - Chemical and Drug Induced Liver Injury/enzymology/*pathology
MH  - Drug Synergism
MH  - Electrophoretic Mobility Shift Assay
MH  - Ethanol/*toxicity
MH  - Fever/*chemically induced/physiopathology
MH  - Glutathione/metabolism
MH  - Hallucinogens/*toxicity
MH  - Lipid Peroxidation/drug effects
MH  - Liver/enzymology/pathology
MH  - Male
MH  - Mice
MH  - Microscopy, Electron, Transmission
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - NF-kappa B/metabolism
MH  - Organ Size/drug effects
MH  - Oxidative Stress/drug effects
MH  - Protein Carbonylation/drug effects
EDAT- 2008/09/02 09:00
MHDA- 2009/01/06 09:00
CRDT- 2008/09/02 09:00
PHST- 2008/06/17 00:00 [received]
PHST- 2008/07/24 00:00 [revised]
PHST- 2008/07/26 00:00 [accepted]
PHST- 2008/09/02 09:00 [pubmed]
PHST- 2009/01/06 09:00 [medline]
PHST- 2008/09/02 09:00 [entrez]
AID - S0300-483X(08)00369-7 [pii]
AID - 10.1016/j.tox.2008.07.064 [doi]
PST - ppublish
SO  - Toxicology. 2008 Oct 30;252(1-3):64-71. doi: 10.1016/j.tox.2008.07.064. Epub 2008 
      Aug 7.