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Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose
The aim of this study is to analyse cardiac specimens from human cocaine-related overdose, to verify the hypothesis that cardiac toxicity by acute exposure to high dosage of cocaine could be mediated by unbalanced myocardial oxidative stress, and to evaluate the apoptotic response. To address these...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345006/ https://www.ncbi.nlm.nih.gov/pubmed/28281685 http://dx.doi.org/10.1038/srep44262 |
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author | Turillazzi, Emanuela Cerretani, Daniela Cantatore, Santina Fiaschi, Anna Ida Frati, Paola Micheli, Lucia Neri, Margherita Cipolloni, Luigi Di Paolo, Marco Pinchi, Enrica Riezzo, Irene Santurro, Alessandro Vullo, Annamaria Fineschi, Vittorio |
author_facet | Turillazzi, Emanuela Cerretani, Daniela Cantatore, Santina Fiaschi, Anna Ida Frati, Paola Micheli, Lucia Neri, Margherita Cipolloni, Luigi Di Paolo, Marco Pinchi, Enrica Riezzo, Irene Santurro, Alessandro Vullo, Annamaria Fineschi, Vittorio |
author_sort | Turillazzi, Emanuela |
collection | PubMed |
description | The aim of this study is to analyse cardiac specimens from human cocaine-related overdose, to verify the hypothesis that cardiac toxicity by acute exposure to high dosage of cocaine could be mediated by unbalanced myocardial oxidative stress, and to evaluate the apoptotic response. To address these issues, biochemical and immunohistological markers of oxidative/nitrosative stress were evaluated. We found that i-NOS, NOX2 and nitrotyrosine expression were significantly higher in the hearts of subjects who had died from high doses of cocaine, compared to the control group. Increase of these markers was associated with a dramatic increase in 8-OHdG, another marker of oxidative stress. A high number of TUNEL-positive apoptotic myocells was observed in the study group compared to the control group. The immunoexpression of TNF-α was significantly higher in the cocaine group compared to the control group. Furthermore, we detected a significantly stronger immunoresponse to anti-SMAC/DIABLO in our study group compared to control cases. Both cardiac Fas-dependent and mitochondria-dependent apoptotic pathways appeared to be activated to a greater extent in the cocaine group than in the control group. Our results highlight the central role of oxidative stress in cocaine toxicity. High levels of NOS can promote the oxidation process and lead to apoptosis. |
format | Online Article Text |
id | pubmed-5345006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53450062017-03-14 Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose Turillazzi, Emanuela Cerretani, Daniela Cantatore, Santina Fiaschi, Anna Ida Frati, Paola Micheli, Lucia Neri, Margherita Cipolloni, Luigi Di Paolo, Marco Pinchi, Enrica Riezzo, Irene Santurro, Alessandro Vullo, Annamaria Fineschi, Vittorio Sci Rep Article The aim of this study is to analyse cardiac specimens from human cocaine-related overdose, to verify the hypothesis that cardiac toxicity by acute exposure to high dosage of cocaine could be mediated by unbalanced myocardial oxidative stress, and to evaluate the apoptotic response. To address these issues, biochemical and immunohistological markers of oxidative/nitrosative stress were evaluated. We found that i-NOS, NOX2 and nitrotyrosine expression were significantly higher in the hearts of subjects who had died from high doses of cocaine, compared to the control group. Increase of these markers was associated with a dramatic increase in 8-OHdG, another marker of oxidative stress. A high number of TUNEL-positive apoptotic myocells was observed in the study group compared to the control group. The immunoexpression of TNF-α was significantly higher in the cocaine group compared to the control group. Furthermore, we detected a significantly stronger immunoresponse to anti-SMAC/DIABLO in our study group compared to control cases. Both cardiac Fas-dependent and mitochondria-dependent apoptotic pathways appeared to be activated to a greater extent in the cocaine group than in the control group. Our results highlight the central role of oxidative stress in cocaine toxicity. High levels of NOS can promote the oxidation process and lead to apoptosis. Nature Publishing Group 2017-03-10 /pmc/articles/PMC5345006/ /pubmed/28281685 http://dx.doi.org/10.1038/srep44262 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Turillazzi, Emanuela Cerretani, Daniela Cantatore, Santina Fiaschi, Anna Ida Frati, Paola Micheli, Lucia Neri, Margherita Cipolloni, Luigi Di Paolo, Marco Pinchi, Enrica Riezzo, Irene Santurro, Alessandro Vullo, Annamaria Fineschi, Vittorio Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose |
title | Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose |
title_full | Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose |
title_fullStr | Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose |
title_full_unstemmed | Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose |
title_short | Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose |
title_sort | myocardial oxidative damage is induced by cardiac fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345006/ https://www.ncbi.nlm.nih.gov/pubmed/28281685 http://dx.doi.org/10.1038/srep44262 |
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