PMID- 20170704
OWN - NLM
STAT- MEDLINE
DCOM- 20100420
LR  - 20141120
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 270
IP  - 2-3
DP  - 2010 Apr 11
TI  - Metabolic interactions between ethanol and MDMA in primary cultured rat 
      hepatocytes.
PG  - 150-7
LID - 10.1016/j.tox.2010.02.010 [doi]
AB  - 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy), a drug of abuse commonly 
      consumed at rave parties, is often taken in a polydrug abuse scenario, ethanol 
      being one of the most associated drugs. Both MDMA and ethanol are mainly 
      metabolized in the liver with formation of toxic metabolites. Our working 
      hypothesis is that ethanol can modify the metabolism of MDMA through the 
      cytochrome P450 system, and that this effect may be further potentiated by 
      hyperthermia, a well-known consequence of MDMA abuse. To investigate these 
      putative interactions we used primary rat hepatocyte cultures, which were exposed 
      to 300 mM ethanol, 1.6 mM MDMA and the combination of both, at normothermic (36.5 
      degrees C) and hyperthermic (40.5 degrees C) conditions. After 24 h, the levels 
      of MDA, HMA and HMMA in the cell culture medium were quantified by GC/MS. In 
      addition, we repeated the same experimental design preceded by 1h incubation with 
      0.18 microM ketoconazole or 150 microM diallyl sulphide (CYP3A and CYP2E1 
      inhibitors, respectively), to evaluate the putative role of these isoenzymes in 
      the observed effects. The results obtained showed that ethanol exposure increases 
      the formation of some MDMA metabolites such as HMA (1.8 times increase) and MDA 
      (1.5 times increase). This effect was markedly increased under hyperthermic 
      conditions (HMA, MDA and HMMA formation increased 10, 6 and 16 times, 
      respectively) and is mediated, at least partially, by CYP3A and CYP2E1.
CI  - Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
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 - de Pinho, Paula Guedes
AU  - de Pinho PG
FAU - Fernandes, Eduarda
AU  - Fernandes E
FAU - Branco, Paula Serio
AU  - Branco PS
FAU - Ferreira, Luisa Maria
AU  - Ferreira LM
FAU - Carmo, Helena
AU  - Carmo H
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 - 20100217
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Hallucinogens)
RN  - 3K9958V90M (Ethanol)
RN  - 63231-63-0 (RNA)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2E1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Biotransformation
MH  - Cell Death/drug effects
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Central Nervous System Depressants/*metabolism/*toxicity
MH  - Cytochrome P-450 CYP2E1/metabolism
MH  - Cytochrome P-450 CYP3A/metabolism
MH  - Drug Interactions
MH  - Ethanol/*metabolism/*toxicity
MH  - Gas Chromatography-Mass Spectrometry
MH  - Hallucinogens/*metabolism/*toxicity
MH  - Hepatocytes/*drug effects/enzymology/*metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*metabolism/*toxicity
MH  - Oxidation-Reduction
MH  - RNA/biosynthesis/isolation & purification
MH  - Rats
MH  - Rats, Wistar
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2010/02/23 06:00
MHDA- 2010/04/21 06:00
CRDT- 2010/02/23 06:00
PHST- 2009/12/22 00:00 [received]
PHST- 2010/02/09 00:00 [revised]
PHST- 2010/02/10 00:00 [accepted]
PHST- 2010/02/23 06:00 [entrez]
PHST- 2010/02/23 06:00 [pubmed]
PHST- 2010/04/21 06:00 [medline]
AID - S0300-483X(10)00084-3 [pii]
AID - 10.1016/j.tox.2010.02.010 [doi]
PST - ppublish
SO  - Toxicology. 2010 Apr 11;270(2-3):150-7. doi: 10.1016/j.tox.2010.02.010. Epub 2010 
      Feb 17.