PMID- 18848861
OWN - NLM
STAT- MEDLINE
DCOM- 20090115
LR  - 20131121
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 254
IP  - 1-2
DP  - 2008 Dec 5
TI  - Synergistic toxicity of ethanol and MDMA towards primary cultured rat 
      hepatocytes.
PG  - 42-50
LID - 10.1016/j.tox.2008.09.009 [doi]
AB  - Ethanol is frequently consumed along with 3,4-methylenedioxymethamphetamine 
      (MDMA; ecstasy). Since both compounds are hepatotoxic and are metabolized in the 
      liver, an increased deleterious interaction resulting from the concomitant use of 
      these two drugs seems plausible. Another important feature of MDMA-induced 
      toxicity is hyperthermia, an effect known to be potentiated after continuous 
      exposure to ethanol. Considering the potential deleterious interaction, the aim 
      of the present study was to evaluate the hepatotoxic effects of ethanol and MDMA 
      mixtures to primary cultured rat hepatocytes and to elucidate the mechanism(s) 
      underlying this interaction. For this purpose, the toxicity induced by MDMA to 
      primary cultured rat hepatocytes in absence or in presence of ethanol was 
      evaluated, under normothermic (36.5 degrees C) and hyperthermic (40.5 degrees C) 
      conditions. While MDMA and ethanol, by themselves, had discrete effects on the 
      analysed parameters, which were slightly aggravated under hyperthermia, the 
      simultaneous incubation of MDMA and ethanol for 24h, resulted in high cell death 
      ratios accompanied by a significant disturbance of cellular redox status and 
      decreased energy levels. Evaluation of apoptotic/necrotic features provided clear 
      evidences that the cell death occurs preferentially through a necrotic pathway. 
      All the evaluated parameters were dramatically aggravated when cells were 
      incubated under hyperthermia. In conclusion, co-exposure of hepatocytes to 
      ethanol and MDMA definitely results in a synergism of the hepatotoxic effects, 
      through a disruption of the cellular redox status and enhanced cell death by a 
      necrotic pathway in a temperature-dependent extent.
FAU - Pontes, Helena
AU  - Pontes H
AD  - REQUIMTE, Toxicology Department, Faculty of Pharmacy, University of Porto, Rua 
      Anibal Cunha 164, 4099-030 Porto, Portugal.
FAU - Sousa, Carla
AU  - Sousa C
FAU - Silva, Renata
AU  - Silva R
FAU - Fernandes, Eduarda
AU  - Fernandes E
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 - 20080920
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 3K9958V90M (Ethanol)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Drug Synergism
MH  - Ethanol/*toxicity
MH  - Hepatocytes/*drug effects
MH  - Hot Temperature
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Oxidative Stress
MH  - Rats
MH  - Rats, Wistar
EDAT- 2008/10/14 09:00
MHDA- 2009/01/16 09:00
CRDT- 2008/10/14 09:00
PHST- 2008/07/14 00:00 [received]
PHST- 2008/09/03 00:00 [revised]
PHST- 2008/09/04 00:00 [accepted]
PHST- 2008/10/14 09:00 [pubmed]
PHST- 2009/01/16 09:00 [medline]
PHST- 2008/10/14 09:00 [entrez]
AID - S0300-483X(08)00432-0 [pii]
AID - 10.1016/j.tox.2008.09.009 [doi]
PST - ppublish
SO  - Toxicology. 2008 Dec 5;254(1-2):42-50. doi: 10.1016/j.tox.2008.09.009. Epub 2008 
      Sep 20.