PMID- 20138954
OWN - NLM
STAT- MEDLINE
DCOM- 20100420
LR  - 20171116
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 270
IP  - 2-3
DP  - 2010 Apr 11
TI  - Comparative effects of 3,4-methylenedioxymethamphetamine and 
      4-methylthioamphetamine on rat liver mitochondrial function.
PG  - 99-105
LID - 10.1016/j.tox.2010.01.022 [doi]
AB  - Ecstasy, which is used as a recreational drug, is a common street name for 3, 
      4-methylenedioxymethamphetamine (MDMA). Another drug of abuse chemically related, 
      though less common than MDMA, is the amphetamine derivative 
      4-methylthioamphetamine (MTA). MDMA and MTA induce different systemic and 
      organ-specific effects, including neurotoxicity, hyperthermia, nephrotoxicity, 
      cardiotoxicity and hepatotoxicity. Therefore, it is clear that MDMA and MTA are 
      responsible for inducing organ toxicity. The mechanisms underlying MDMA and 
      MTA-induced hepatotoxicity are multifactorial, and therefore not completely 
      understood. Recent findings indicate interference with cellular bioenergetics as 
      an important toxicological feature of ecstasy. However, less is known about the 
      involvement of mitochondria in MTA-induced hepatotoxicity. Thus, we compared the 
      direct influence of MDMA and MTA on rat liver mitochondrial function 
      [mitochondrial permeability transition (MPT), mitochondrial oxidative stress, and 
      mitochondrial bioenergetics]. It was shown that MTA (from 0.025 up to 0.1mM) was 
      more potent than MDMA (from 0.2 up to 0.5mM) in decreasing the sensitivity of rat 
      liver mitochondria to MPT. However, higher concentrations of MTA (from 0.5 up to 
      2mM) were highly toxic to mitochondria. MTA simultaneously increased H(2)O(2) 
      production in a monoamine oxidase (MAO)-dependent way, and uncoupled and 
      inhibited mitochondrial respiration. In contrast, MDMA had only limited or no 
      effects on these mitochondrial parameters. According to these results, it is 
      possible to postulate that, depending on the concentration, MTA can potentially 
      be more efficient in its effects on liver mitochondria than MDMA and, also, that 
      its harmful effects may contribute to its hepatotoxicity.
CI  - Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Custodio, Jose B A
AU  - Custodio JB
AD  - CNC, Laboratorio de Bioquimica, Faculdade de Farmacia, Universidade de Coimbra, 
      3000-295 Coimbra, Portugal.
FAU - Santos, Maria S
AU  - Santos MS
FAU - Goncalves, Dalia I R
AU  - Goncalves DI
FAU - Moreno, Antonio J M
AU  - Moreno AJ
FAU - Fernandes, Eduarda
AU  - Fernandes E
FAU - Bastos, Maria L
AU  - Bastos ML
FAU - Carvalho, Felix
AU  - Carvalho F
FAU - Vicente, Joaquim A F
AU  - Vicente JA
FAU - Fernandes, Maria A S
AU  - Fernandes MA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100206
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Amphetamines)
RN  - 0 (Hallucinogens)
RN  - 0 (Sulfhydryl Compounds)
RN  - 6JP2T8KXTR (4-methylthioamphetamine)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/*toxicity
MH  - Amphetamines/*toxicity
MH  - Animals
MH  - Energy Metabolism/drug effects
MH  - Hallucinogens/*toxicity
MH  - Hepatocytes/drug effects
MH  - Hydrogen Peroxide/metabolism
MH  - In Vitro Techniques
MH  - Male
MH  - Membrane Potentials/drug effects
MH  - Mitochondria, Liver/*drug effects/*metabolism
MH  - Mitochondrial Membranes/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Oxygen Consumption/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Sulfhydryl Compounds/metabolism
EDAT- 2010/02/09 06:00
MHDA- 2010/04/21 06:00
CRDT- 2010/02/09 06:00
PHST- 2009/12/14 00:00 [received]
PHST- 2010/01/29 00:00 [revised]
PHST- 2010/01/29 00:00 [accepted]
PHST- 2010/02/09 06:00 [entrez]
PHST- 2010/02/09 06:00 [pubmed]
PHST- 2010/04/21 06:00 [medline]
AID - S0300-483X(10)00033-8 [pii]
AID - 10.1016/j.tox.2010.01.022 [doi]
PST - ppublish
SO  - Toxicology. 2010 Apr 11;270(2-3):99-105. doi: 10.1016/j.tox.2010.01.022. Epub 
      2010 Feb 6.