The effects of ecstasy (MDMA) on rat liver bioenergetics

Daniel Rusyniak, Stephany L. Tandy, Lisa M. Kamendulis, Jon E. Sprague, James E. Klaunig

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objectives Use of the drug ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) can result in life-threatening hyperthermia. Agents that uncouple mitochondrial oxidative phosphorylation are known to cause severe hyperthermia. In the present study, the authors tested the hypothesis that MDMA directly uncouples oxidative phosphorylation in rat liver mitochondria. Methods Effects on mitochondrial bioenergetics were assessed both in vitro and ex vivo. In vitro studies consisted of measuring the effects of MDMA (0.1-5.0 mmol/L) on states of respiration in isolated rat liver mitochondria and on mitochondrial membrane potential in a rat liver cell line. In ex vivo studies, mitochondrial rates of respiration were measured in the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously). Results With the in vitro mitochondrial preparations, only concentrations of 5 mmol/L MDMA showed evidence of uncoupling with a slight increase in state 4 respiration and a corresponding decrease in the respiratory control index. MDMA (0.1-5.0 mmol/L) failed to decrease the mitochondrial membrane potential in 3,3-dihexyloxacarbocyanide iodide-stained WB-344 cells after either one or 24 hours of incubation. Ex vivo rates of respiration obtained from the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously) showed no evidence of mitochondrial uncoupling. Conclusions These data suggest that while high concentrations of MDMA have some mild uncoupling effects in isolated mitochondria, these effects do not translate to cell culture or ex vivo studies in treated animals. These data do not support the view that the hyperthermia induced by MDMA is from a direct effect on mitochondrial oxidative phosphorylation.

Original languageEnglish
Pages (from-to)723-729
Number of pages7
JournalAcademic Emergency Medicine
Volume11
Issue number7
DOIs
StatePublished - Jul 2004

Fingerprint

N-Methyl-3,4-methylenedioxyamphetamine
Energy Metabolism
Liver
Oxidative Phosphorylation
Liver Mitochondrion
Mitochondrial Membrane Potential
Respiratory Rate
Respiration
Fever
Induced Hyperthermia
Iodides
Mitochondria
Cell Culture Techniques

Keywords

  • 3,4-methylenedioxymethamphetamine
  • amphetamines
  • liver
  • mitochondria
  • oxidative phosphorylation
  • uncoupling agents

ASJC Scopus subject areas

  • Emergency Medicine

Cite this

Rusyniak, D., Tandy, S. L., Kamendulis, L. M., Sprague, J. E., & Klaunig, J. E. (2004). The effects of ecstasy (MDMA) on rat liver bioenergetics. Academic Emergency Medicine, 11(7), 723-729. https://doi.org/10.1197/j.aem.2004.03.004

The effects of ecstasy (MDMA) on rat liver bioenergetics. / Rusyniak, Daniel; Tandy, Stephany L.; Kamendulis, Lisa M.; Sprague, Jon E.; Klaunig, James E.

In: Academic Emergency Medicine, Vol. 11, No. 7, 07.2004, p. 723-729.

Research output: Contribution to journalArticle

Rusyniak, D, Tandy, SL, Kamendulis, LM, Sprague, JE & Klaunig, JE 2004, 'The effects of ecstasy (MDMA) on rat liver bioenergetics', Academic Emergency Medicine, vol. 11, no. 7, pp. 723-729. https://doi.org/10.1197/j.aem.2004.03.004
Rusyniak, Daniel ; Tandy, Stephany L. ; Kamendulis, Lisa M. ; Sprague, Jon E. ; Klaunig, James E. / The effects of ecstasy (MDMA) on rat liver bioenergetics. In: Academic Emergency Medicine. 2004 ; Vol. 11, No. 7. pp. 723-729.
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abstract = "Objectives Use of the drug ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) can result in life-threatening hyperthermia. Agents that uncouple mitochondrial oxidative phosphorylation are known to cause severe hyperthermia. In the present study, the authors tested the hypothesis that MDMA directly uncouples oxidative phosphorylation in rat liver mitochondria. Methods Effects on mitochondrial bioenergetics were assessed both in vitro and ex vivo. In vitro studies consisted of measuring the effects of MDMA (0.1-5.0 mmol/L) on states of respiration in isolated rat liver mitochondria and on mitochondrial membrane potential in a rat liver cell line. In ex vivo studies, mitochondrial rates of respiration were measured in the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously). Results With the in vitro mitochondrial preparations, only concentrations of 5 mmol/L MDMA showed evidence of uncoupling with a slight increase in state 4 respiration and a corresponding decrease in the respiratory control index. MDMA (0.1-5.0 mmol/L) failed to decrease the mitochondrial membrane potential in 3,3-dihexyloxacarbocyanide iodide-stained WB-344 cells after either one or 24 hours of incubation. Ex vivo rates of respiration obtained from the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously) showed no evidence of mitochondrial uncoupling. Conclusions These data suggest that while high concentrations of MDMA have some mild uncoupling effects in isolated mitochondria, these effects do not translate to cell culture or ex vivo studies in treated animals. These data do not support the view that the hyperthermia induced by MDMA is from a direct effect on mitochondrial oxidative phosphorylation.",
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