Contribution of oxidative metabolism to cocaine-induced liver and kidney damage
Autor(a) principal: | |
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Data de Publicação: | 2012 |
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/10284/10041 |
Resumo: | Cocaine is a potent psychoactive illicit substance and its abuse represents a major health burden worldwide. The pharmacodynamics and toxicity of cocaine have been extensively documented, and are generally associated to its affinity towards neurotransmitters transporters and several receptors. However, drug-related formation of reactive compounds, as is the case of pro-oxidant reactive species, and interaction at molecular level is still an understudied matter. The involvement of oxidative stress (OS) in cocaine-induced toxicity has been reported in both human and animal models, in several organs and systems, including heart, liver, kidney, and central nervous system (CNS). Cytochrome P450 (CYP450)-mediated cocaine metabolism yields the reactive pro-oxidant compound norcocaine (NCOC) and further oxidative metabolites. Special emphasis should be given to the stable radical norcocaine nitroxide (NCOC-NO·), which plays a key role in cocaine-induced hepatotoxicity, either by entering a futile redox cycle with an N-oxidative metabolite, or by being further oxidized to a highly reactive ion. In fact, cocaine-induced generation of reactive oxygen species (ROS) and consequent OS has been postulated based on the reactivity of cocaine N-oxidative metabolites. Depletion of cellular antioxidant defenses and impairment of mitochondrial respiration have also been considered important causes of ROS production, and subsequent cell death mediated by cocaine. The present review provides a thorough description of the current knowledge on cocaine oxidative metabolism and its role on drug-induced liver and kidney damage. |
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Contribution of oxidative metabolism to cocaine-induced liver and kidney damageCocaineMetabolismOxidative stressLiverKidneyToxicityCocaine is a potent psychoactive illicit substance and its abuse represents a major health burden worldwide. The pharmacodynamics and toxicity of cocaine have been extensively documented, and are generally associated to its affinity towards neurotransmitters transporters and several receptors. However, drug-related formation of reactive compounds, as is the case of pro-oxidant reactive species, and interaction at molecular level is still an understudied matter. The involvement of oxidative stress (OS) in cocaine-induced toxicity has been reported in both human and animal models, in several organs and systems, including heart, liver, kidney, and central nervous system (CNS). Cytochrome P450 (CYP450)-mediated cocaine metabolism yields the reactive pro-oxidant compound norcocaine (NCOC) and further oxidative metabolites. Special emphasis should be given to the stable radical norcocaine nitroxide (NCOC-NO·), which plays a key role in cocaine-induced hepatotoxicity, either by entering a futile redox cycle with an N-oxidative metabolite, or by being further oxidized to a highly reactive ion. In fact, cocaine-induced generation of reactive oxygen species (ROS) and consequent OS has been postulated based on the reactivity of cocaine N-oxidative metabolites. Depletion of cellular antioxidant defenses and impairment of mitochondrial respiration have also been considered important causes of ROS production, and subsequent cell death mediated by cocaine. The present review provides a thorough description of the current knowledge on cocaine oxidative metabolism and its role on drug-induced liver and kidney damage.Bentham Science PublishersRepositório Institucional da Universidade Fernando PessoaValente, M.J.Carvalho, F.Bastos, M.d.L.de Pinho, P.G.Carvalho, Márcia2021-07-02T16:23:11Z2012-01-01T00:00:00Z2012-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10284/10041eng0929-867310.2174/0929867128039889381875-533Xmetadata only accessinfo: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:RCAAP2022-09-06T02:09:20Zoai:bdigital.ufp.pt:10284/10041Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:46:48.916798Repositório 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 |
Contribution of oxidative metabolism to cocaine-induced liver and kidney damage |
title |
Contribution of oxidative metabolism to cocaine-induced liver and kidney damage |
spellingShingle |
Contribution of oxidative metabolism to cocaine-induced liver and kidney damage Valente, M.J. Cocaine Metabolism Oxidative stress Liver Kidney Toxicity |
title_short |
Contribution of oxidative metabolism to cocaine-induced liver and kidney damage |
title_full |
Contribution of oxidative metabolism to cocaine-induced liver and kidney damage |
title_fullStr |
Contribution of oxidative metabolism to cocaine-induced liver and kidney damage |
title_full_unstemmed |
Contribution of oxidative metabolism to cocaine-induced liver and kidney damage |
title_sort |
Contribution of oxidative metabolism to cocaine-induced liver and kidney damage |
author |
Valente, M.J. |
author_facet |
Valente, M.J. Carvalho, F. Bastos, M.d.L. de Pinho, P.G. Carvalho, Márcia |
author_role |
author |
author2 |
Carvalho, F. Bastos, M.d.L. de Pinho, P.G. Carvalho, Márcia |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Repositório Institucional da Universidade Fernando Pessoa |
dc.contributor.author.fl_str_mv |
Valente, M.J. Carvalho, F. Bastos, M.d.L. de Pinho, P.G. Carvalho, Márcia |
dc.subject.por.fl_str_mv |
Cocaine Metabolism Oxidative stress Liver Kidney Toxicity |
topic |
Cocaine Metabolism Oxidative stress Liver Kidney Toxicity |
description |
Cocaine is a potent psychoactive illicit substance and its abuse represents a major health burden worldwide. The pharmacodynamics and toxicity of cocaine have been extensively documented, and are generally associated to its affinity towards neurotransmitters transporters and several receptors. However, drug-related formation of reactive compounds, as is the case of pro-oxidant reactive species, and interaction at molecular level is still an understudied matter. The involvement of oxidative stress (OS) in cocaine-induced toxicity has been reported in both human and animal models, in several organs and systems, including heart, liver, kidney, and central nervous system (CNS). Cytochrome P450 (CYP450)-mediated cocaine metabolism yields the reactive pro-oxidant compound norcocaine (NCOC) and further oxidative metabolites. Special emphasis should be given to the stable radical norcocaine nitroxide (NCOC-NO·), which plays a key role in cocaine-induced hepatotoxicity, either by entering a futile redox cycle with an N-oxidative metabolite, or by being further oxidized to a highly reactive ion. In fact, cocaine-induced generation of reactive oxygen species (ROS) and consequent OS has been postulated based on the reactivity of cocaine N-oxidative metabolites. Depletion of cellular antioxidant defenses and impairment of mitochondrial respiration have also been considered important causes of ROS production, and subsequent cell death mediated by cocaine. The present review provides a thorough description of the current knowledge on cocaine oxidative metabolism and its role on drug-induced liver and kidney damage. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-01-01T00:00:00Z 2012-01-01T00:00:00Z 2021-07-02T16:23:11Z |
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/10284/10041 |
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http://hdl.handle.net/10284/10041 |
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eng |
language |
eng |
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0929-8673 10.2174/092986712803988938 1875-533X |
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metadata only access info:eu-repo/semantics/openAccess |
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metadata only access |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Bentham Science Publishers |
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Bentham Science Publishers |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799130334722260992 |