PMID- 10395044
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20190921
IS  - 0106-9543 (Print)
IS  - 0106-9543 (Linking)
VI  - 19
IP  - 3
DP  - 1999 Jun
TI  - 3,4-Methylenedioxymethamphetamine (ecstasy)-induced hepatotoxicity: effect on 
      cytosolic calcium signals in isolated hepatocytes.
PG  - 234-41
AB  - AIMS/BACKGROUND: Hepatocellular damage has been reported as a consequence of 
      3,4-methylenedioxymethamphetamine (MDMA) intake. However, little is known about 
      the cellular mechanisms involved. The present study was undertaken to evaluate 
      the effects of MDMA on cell viability as well as free calcium levels ([Ca2+]i) in 
      short-term cultured hepatocytes. Reduced glutathione (GSH), 
      adenosine-5'-triphosphate (ATP) and lipid peroxidation were investigated to 
      evaluate the toxic effect of MDMA, in vitro, using freshly isolated rat 
      hepatocytes. METHODS: In order to measure cytosolic free Ca2+ concentrations 
      ([Ca2+]i), rat hepatocytes were loaded with the Ca2+ indicator 
      fura-2-acetoxymethylester (fura-2-AM). RESULTS: A sustained rise of ([Ca2+]i) 
      after incubation with MDMA was the most noteworthy finding. In Ca2+-free medium, 
      MDMA caused a reduced increase of ([Ca2+]i). On the other hand, MDMA (0.1-5 mM) 
      induced a concentration-dependent and time exposure-dependent GSH and ATP 
      depletion. Although it did not reach statistical significance, GSH deficits were 
      accompanied by a tendency to increase lipid peroxidation 3 h after MDMA 
      incubation. CONCLUSIONS: The above data suggest that the marked rise of ([Ca2+]i) 
      and subsequent ATP and GSH depletion can lead to a rapid decrease in cell 
      viability.
FAU - Beitia, G
AU  - Beitia G
AD  - Department of Pharmacology, University of Navarra, Pamplona, Spain.
FAU - Cobreros, A
AU  - Cobreros A
FAU - Sainz, L
AU  - Sainz L
FAU - Cenarruzabeitia, E
AU  - Cenarruzabeitia E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - Liver
JT  - Liver
JID - 8200939
RN  - 11000-17-2 (Vasopressins)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.6.1.- (Transaminases)
RN  - GAN16C9B8O (Glutathione)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium Signaling/*drug effects
MH  - Cell Membrane/metabolism
MH  - Cells, Cultured
MH  - Cytosol/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Egtazic Acid/pharmacology
MH  - Glutathione/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Lipid Peroxidation/drug effects
MH  - Liver/cytology/*drug effects/enzymology/*metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Rats
MH  - Rats, Wistar
MH  - Time Factors
MH  - Transaminases/metabolism
MH  - Vasopressins/pharmacology
EDAT- 1999/07/08 00:00
MHDA- 1999/07/08 00:01
CRDT- 1999/07/08 00:00
PHST- 1999/07/08 00:00 [pubmed]
PHST- 1999/07/08 00:01 [medline]
PHST- 1999/07/08 00:00 [entrez]
AID - 10.1111/j.1478-3231.1999.tb00041.x [doi]
PST - ppublish
SO  - Liver. 1999 Jun;19(3):234-41. doi: 10.1111/j.1478-3231.1999.tb00041.x.