PMID- 20599925
OWN - NLM
STAT- MEDLINE
DCOM- 20101228
LR  - 20161125
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 643
IP  - 2-3
DP  - 2010 Sep 25
TI  - Involvement of mitochondrial/lysosomal toxic cross-talk in ecstasy induced liver 
      toxicity under hyperthermic condition.
PG  - 162-9
LID - 10.1016/j.ejphar.2010.06.019 [doi]
AB  - The initial objectives of this study were to evaluate the extent of 3, 
      4-methylenedioxymethamphetamine (MDMA) induced loss of cell viability 
      (cytotoxicity), induction of reactive oxygen species formation and damage to 
      sub-cellular organelles (e.g. mitochondria/lysosomes) in freshly isolated rat 
      hepatocytes under normothermic conditions (37 degrees C) and to compare the 
      results with the effects obtained under hyperthermic conditions (41 degrees C). 
      MDMA induced cytotoxicity, reactive oxygen species formation, mitochondrial 
      membrane potential decline and lysosomal membrane leakiness in isolated rat 
      hepatocytes at 37 degrees C. A rise in incubation temperature from 37 degrees C 
      to 41 degrees C had an additive/synergic effect on the oxidative stress markers. 
      We observed variations in mitochondrial membrane potential and lysosomal membrane 
      stability that are significantly (P<0.05) higher than those under normothermic 
      conditions. Antioxidants, reactive oxygen species scavengers, lysosomal 
      inactivators, mitochondrial permeability transition (MPT) pore sealing agents, 
      NADPH P450 reductase inhibitor, and inhibitors of reduced CYP2E1 and CYP2D6 
      prevented all MDMA induced hepatocyte oxidative stress cytotoxicity markers. It 
      is therefore suggested that metabolic reductive activation of MDMA by reduced 
      cytochrome P450s and glutathione could lead to generation of some biological 
      reactive intermediates which could activate reactive oxygen species generation 
      and cause mitochondrial and lysosomal oxidative stress membrane damages. We 
      finally concluded that hyperthermia could potentiate MDMA induced liver toxicity 
      probably through a mitochondrial/lysosomal toxic cross-talk in freshly isolated 
      rat hepatocytes.
CI  - 2010 Elsevier B.V. All rights reserved.
FAU - Pourahmad, Jalal
AU  - Pourahmad J
AD  - Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, 
      Iran. j.pourahmadjaktaji@utoronto.ca
FAU - Eskandari, Mohammad Reza
AU  - Eskandari MR
FAU - Nosrati, Masoumeh
AU  - Nosrati M
FAU - Kobarfard, Farzad
AU  - Kobarfard F
FAU - Khajeamiri, Ali Reza
AU  - Khajeamiri AR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100620
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Cytochrome P-450 CYP2D6 Inhibitors)
RN  - 0 (Cytochrome P-450 CYP2E1 Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hallucinogens)
RN  - 0 (Reactive Oxygen Species)
RN  - GAN16C9B8O (Glutathione)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Chemical and Drug Induced Liver Injury/*metabolism/prevention & control
MH  - Cytochrome P-450 CYP2D6 Inhibitors
MH  - Cytochrome P-450 CYP2E1 Inhibitors
MH  - Enzyme Inhibitors/pharmacology
MH  - Glutathione/antagonists & inhibitors
MH  - Hallucinogens/metabolism/*toxicity
MH  - Hepatocytes/drug effects/metabolism
MH  - Hot Temperature/*adverse effects
MH  - Lysosomes/*drug effects/metabolism
MH  - Male
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria, Liver/*drug effects/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/metabolism/*toxicity
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/antagonists & inhibitors/metabolism
MH  - Time Factors
EDAT- 2010/07/06 06:00
MHDA- 2010/12/29 06:00
CRDT- 2010/07/06 06:00
PHST- 2010/01/06 00:00 [received]
PHST- 2010/06/09 00:00 [revised]
PHST- 2010/06/10 00:00 [accepted]
PHST- 2010/07/06 06:00 [entrez]
PHST- 2010/07/06 06:00 [pubmed]
PHST- 2010/12/29 06:00 [medline]
AID - S0014-2999(10)00589-3 [pii]
AID - 10.1016/j.ejphar.2010.06.019 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2010 Sep 25;643(2-3):162-9. doi: 10.1016/j.ejphar.2010.06.019. 
      Epub 2010 Jun 20.