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A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA)

3,4-Methylenedioxymethamphetamine (MDMA or “ecstasy”) is a drug of abuse used by millions worldwide. MDMA human abuse and dependence is well described, but addictive properties are not always consistent among studies. This amphetamine is a substrate type releaser, binding to monoamine transporters,...

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Autores principales: Capela, João Paulo, Carvalho, Félix Dias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149009/
https://www.ncbi.nlm.nih.gov/pubmed/35651589
http://dx.doi.org/10.1016/j.crtox.2022.100075
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author Capela, João Paulo
Carvalho, Félix Dias
author_facet Capela, João Paulo
Carvalho, Félix Dias
author_sort Capela, João Paulo
collection PubMed
description 3,4-Methylenedioxymethamphetamine (MDMA or “ecstasy”) is a drug of abuse used by millions worldwide. MDMA human abuse and dependence is well described, but addictive properties are not always consistent among studies. This amphetamine is a substrate type releaser, binding to monoamine transporters, leading to a pronounced release of serotonin and noradrenaline and to a minor extent dopamine. The toxicity of MDMA is well studied at the pre-clinical level, with neurotoxicity and hepatotoxicity being particularly described. In this review, we describe the most relevant MDMA effects at the mitochondrial level found in in vitro and in vivo models, these later conducted in mice and rats. Most of these reports focus on the mitochondria of brain or liver. In in vitro models, MDMA causes depletion of ATP levels and inhibition of mitochondrial complex I and III, loss in mitochondrial membrane potential (ΔΨm) and induction of mitochondrial permeability transition. The involvement of mitochondria in the apoptotic cell death evoked by MDMA has also been shown, such as the release of cytochrome c. Additionally, MDMA or its metabolites impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria. In animal studies, MDMA decreased mitochondrial complex I activity and decreased ATP levels. Moreover, MDMA-evoked oxidative stress has been shown to cause deletion on mitochondrial DNA and impairment in mitochondrial protein synthesis. Although the concentrations and doses used in some studies do not always correlate to the human scenario, the mitochondrial abnormalities evoked by MDMA are well described and are in part responsible for its mechanism of toxicity.
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spelling pubmed-91490092022-05-31 A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA) Capela, João Paulo Carvalho, Félix Dias Curr Res Toxicol Article 3,4-Methylenedioxymethamphetamine (MDMA or “ecstasy”) is a drug of abuse used by millions worldwide. MDMA human abuse and dependence is well described, but addictive properties are not always consistent among studies. This amphetamine is a substrate type releaser, binding to monoamine transporters, leading to a pronounced release of serotonin and noradrenaline and to a minor extent dopamine. The toxicity of MDMA is well studied at the pre-clinical level, with neurotoxicity and hepatotoxicity being particularly described. In this review, we describe the most relevant MDMA effects at the mitochondrial level found in in vitro and in vivo models, these later conducted in mice and rats. Most of these reports focus on the mitochondria of brain or liver. In in vitro models, MDMA causes depletion of ATP levels and inhibition of mitochondrial complex I and III, loss in mitochondrial membrane potential (ΔΨm) and induction of mitochondrial permeability transition. The involvement of mitochondria in the apoptotic cell death evoked by MDMA has also been shown, such as the release of cytochrome c. Additionally, MDMA or its metabolites impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria. In animal studies, MDMA decreased mitochondrial complex I activity and decreased ATP levels. Moreover, MDMA-evoked oxidative stress has been shown to cause deletion on mitochondrial DNA and impairment in mitochondrial protein synthesis. Although the concentrations and doses used in some studies do not always correlate to the human scenario, the mitochondrial abnormalities evoked by MDMA are well described and are in part responsible for its mechanism of toxicity. Elsevier 2022-05-19 /pmc/articles/PMC9149009/ /pubmed/35651589 http://dx.doi.org/10.1016/j.crtox.2022.100075 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Capela, João Paulo
Carvalho, Félix Dias
A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA)
title A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA)
title_full A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA)
title_fullStr A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA)
title_full_unstemmed A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA)
title_short A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA)
title_sort review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, mdma)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149009/
https://www.ncbi.nlm.nih.gov/pubmed/35651589
http://dx.doi.org/10.1016/j.crtox.2022.100075
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