Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity Relationship
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/12872 https://doi.org/10.1021/tx060123i |
Resumo: | The toxicological and redox profiles of MDMA and its major metabolites (MDA, α-methyldopamine, N-methyl-α-methyldopamine, 6-hydroxy-α-methyldopamine, 3-methoxy-α-methyldopamine) were studied to establish a structure-toxicity relationship and determine their individual contribution to cell death induction by apoptosis and/or necrosis. The results of the comparative toxicity study, using undifferentiated PC12 cells, strongly suggest that the metabolites possessing a catecholic group are more toxic to the cells than MDMA and metabolites with at least one protected phenolic group. Redox studies reveal that an oxidative mechanism seems to play an important role in metabolite cytotoxicity. Nuclear features of apoptosis and/or necrosis show that most of the metabolites, particularly N-methyl-α-methyldopamine, induce cell death by apoptosis, largely accompanied by necrotic features. No significant differences were found between MDMA and the metabolites, concerning overall characteristics of cell death. These results may be useful to ascertain the contribution of metabolism in MDMA neurotoxicity molecular mechanisms |
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Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity RelationshipThe toxicological and redox profiles of MDMA and its major metabolites (MDA, α-methyldopamine, N-methyl-α-methyldopamine, 6-hydroxy-α-methyldopamine, 3-methoxy-α-methyldopamine) were studied to establish a structure-toxicity relationship and determine their individual contribution to cell death induction by apoptosis and/or necrosis. The results of the comparative toxicity study, using undifferentiated PC12 cells, strongly suggest that the metabolites possessing a catecholic group are more toxic to the cells than MDMA and metabolites with at least one protected phenolic group. Redox studies reveal that an oxidative mechanism seems to play an important role in metabolite cytotoxicity. Nuclear features of apoptosis and/or necrosis show that most of the metabolites, particularly N-methyl-α-methyldopamine, induce cell death by apoptosis, largely accompanied by necrotic features. No significant differences were found between MDMA and the metabolites, concerning overall characteristics of cell death. These results may be useful to ascertain the contribution of metabolism in MDMA neurotoxicity molecular mechanismsAmerican Chemical Society2006-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/12872http://hdl.handle.net/10316/12872https://doi.org/10.1021/tx060123iengChemical Research in Toxicology. 19:10 (2006) 1294-13040893-228XMilhazes, NunoCunha-Oliveira, TeresaMartins, PedroGarrido, JorgeOliveira, CatarinaRego, A. CristinaBorges, Fernandainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-05-25T04:27:49Zoai:estudogeral.uc.pt:10316/12872Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:43:38.351807Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity Relationship |
title |
Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity Relationship |
spellingShingle |
Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity Relationship Milhazes, Nuno |
title_short |
Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity Relationship |
title_full |
Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity Relationship |
title_fullStr |
Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity Relationship |
title_full_unstemmed |
Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity Relationship |
title_sort |
Synthesis and Cytotoxic Profile of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) and Its Metabolites on Undifferentiated PC12 Cells: A Putative Structure−Toxicity Relationship |
author |
Milhazes, Nuno |
author_facet |
Milhazes, Nuno Cunha-Oliveira, Teresa Martins, Pedro Garrido, Jorge Oliveira, Catarina Rego, A. Cristina Borges, Fernanda |
author_role |
author |
author2 |
Cunha-Oliveira, Teresa Martins, Pedro Garrido, Jorge Oliveira, Catarina Rego, A. Cristina Borges, Fernanda |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Milhazes, Nuno Cunha-Oliveira, Teresa Martins, Pedro Garrido, Jorge Oliveira, Catarina Rego, A. Cristina Borges, Fernanda |
description |
The toxicological and redox profiles of MDMA and its major metabolites (MDA, α-methyldopamine, N-methyl-α-methyldopamine, 6-hydroxy-α-methyldopamine, 3-methoxy-α-methyldopamine) were studied to establish a structure-toxicity relationship and determine their individual contribution to cell death induction by apoptosis and/or necrosis. The results of the comparative toxicity study, using undifferentiated PC12 cells, strongly suggest that the metabolites possessing a catecholic group are more toxic to the cells than MDMA and metabolites with at least one protected phenolic group. Redox studies reveal that an oxidative mechanism seems to play an important role in metabolite cytotoxicity. Nuclear features of apoptosis and/or necrosis show that most of the metabolites, particularly N-methyl-α-methyldopamine, induce cell death by apoptosis, largely accompanied by necrotic features. No significant differences were found between MDMA and the metabolites, concerning overall characteristics of cell death. These results may be useful to ascertain the contribution of metabolism in MDMA neurotoxicity molecular mechanisms |
publishDate |
2006 |
dc.date.none.fl_str_mv |
2006-10 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/12872 http://hdl.handle.net/10316/12872 https://doi.org/10.1021/tx060123i |
url |
http://hdl.handle.net/10316/12872 https://doi.org/10.1021/tx060123i |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Chemical Research in Toxicology. 19:10 (2006) 1294-1304 0893-228X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133708511346688 |