N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure

Detalhes bibliográficos
Autor(a) principal: Reyes, David R.A. [UNESP]
Data de Publicação: 2018
Outros Autores: Gomes, Mariana J. [UNESP], Rosa, Camila M. [UNESP], Pagan, Luana U. [UNESP], Damatto, Felipe C. [UNESP], Damatto, Ricardo L. [UNESP], Depra, Igor [UNESP], Campos, Dijon H.S. [UNESP], Fernandez, Ana A.H. [UNESP], Martinez, Paula F., Okoshi, Katashi [UNESP], Okoshi, Marina P. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1159/000486115
http://hdl.handle.net/11449/175671
Resumo: Background/Aims: To evaluate the effects of the antioxidant N-acetylcysteine (NAC) on cardiac structure and function in rats with long-term ascending aortic stenosis (AS). Methods: Four months after inducing AS, Wistar rats were assigned into the groups Sham, AS, and AS treated with NAC (AS-NAC) and followed for eight weeks. Cardiac structure and function were evaluated by echocardiogram. Myocardial antioxidant enzymes activity was measured by spectrophotometry and malondialdehyde serum concentration by HPLC. Gene expression of NADPH oxidase subunits NOX2, NOX4, p22 phox, and p47 phox was assessed by real time RT-PCR and protein expression of MAPK proteins by Western blot. Statistical analyzes were performed with Goodman and ANOVA or Mann-Whitney Results: NAC restored myocardial total glutathione (Sham 20.8±3.00; AS 12.6±2.92; AS-NAC 17.6±2.45 nmol/g tissue; p<0.05 AS vs Sham and AS-NAC). Malondialdehyde serum concentration was lower in AS-NAC and myocardial lipid hydroperoxide was higher in AS (Sham 199±48.1; AS 301±36.0; AS-NAC 181±41.3 nmol/g tissue). Glutathione peroxidase activity was lower in AS than Sham. Echocardiogram showed LV concentric hypertrophy with systolic and diastolic dysfunction before and after treatment; no differences were observed between AS-NAC and AS groups. NAC reduced p-ERK and p-JNK protein expression, attenuated myocardial fibrosis, and decreased the frequency of right ventricular hypertrophy. Conclusion: N-acetylcysteine restores myocardial total glutathione, reduces systemic and myocardial oxidative stress, improves MAPK signaling, and attenuates myocardial fibrosis in aortic stenosis rats.
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spelling N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart FailureAortic stenosisCardiac failureEchocardiogramMAPKRatTissue Doppler imagingVentricular remodelingBackground/Aims: To evaluate the effects of the antioxidant N-acetylcysteine (NAC) on cardiac structure and function in rats with long-term ascending aortic stenosis (AS). Methods: Four months after inducing AS, Wistar rats were assigned into the groups Sham, AS, and AS treated with NAC (AS-NAC) and followed for eight weeks. Cardiac structure and function were evaluated by echocardiogram. Myocardial antioxidant enzymes activity was measured by spectrophotometry and malondialdehyde serum concentration by HPLC. Gene expression of NADPH oxidase subunits NOX2, NOX4, p22 phox, and p47 phox was assessed by real time RT-PCR and protein expression of MAPK proteins by Western blot. Statistical analyzes were performed with Goodman and ANOVA or Mann-Whitney Results: NAC restored myocardial total glutathione (Sham 20.8±3.00; AS 12.6±2.92; AS-NAC 17.6±2.45 nmol/g tissue; p<0.05 AS vs Sham and AS-NAC). Malondialdehyde serum concentration was lower in AS-NAC and myocardial lipid hydroperoxide was higher in AS (Sham 199±48.1; AS 301±36.0; AS-NAC 181±41.3 nmol/g tissue). Glutathione peroxidase activity was lower in AS than Sham. Echocardiogram showed LV concentric hypertrophy with systolic and diastolic dysfunction before and after treatment; no differences were observed between AS-NAC and AS groups. NAC reduced p-ERK and p-JNK protein expression, attenuated myocardial fibrosis, and decreased the frequency of right ventricular hypertrophy. Conclusion: N-acetylcysteine restores myocardial total glutathione, reduces systemic and myocardial oxidative stress, improves MAPK signaling, and attenuates myocardial fibrosis in aortic stenosis rats.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Internal Medicine Botucatu Medical School Sao Paulo State University UNESPBotucatu Institute of Biosciences Sao Paulo State University UNESPFederal University of Mato Grosso Do sul Campo GrandeFaculdade de Medicina de Botucatu Departamento de Clinica Medica, Rubiao Junior, S/N CEP 18.Department of Internal Medicine Botucatu Medical School Sao Paulo State University UNESPBotucatu Institute of Biosciences Sao Paulo State University UNESPFaculdade de Medicina de Botucatu Departamento de Clinica Medica, Rubiao Junior, S/N CEP 18.FAPESP: 2014/21972-3CNPq: 306770/2015-6CNPq: 308674/2015-4Universidade Estadual Paulista (Unesp)Campo GrandeReyes, David R.A. [UNESP]Gomes, Mariana J. [UNESP]Rosa, Camila M. [UNESP]Pagan, Luana U. [UNESP]Damatto, Felipe C. [UNESP]Damatto, Ricardo L. [UNESP]Depra, Igor [UNESP]Campos, Dijon H.S. [UNESP]Fernandez, Ana A.H. [UNESP]Martinez, Paula F.Okoshi, Katashi [UNESP]Okoshi, Marina P. [UNESP]2018-12-11T17:17:01Z2018-12-11T17:17:01Z2018-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2310-2321application/pdfhttp://dx.doi.org/10.1159/000486115Cellular Physiology and Biochemistry, v. 44, n. 6, p. 2310-2321, 2018.1421-97781015-8987http://hdl.handle.net/11449/17567110.1159/0004861152-s2.0-850386351232-s2.0-85038635123.pdf1590971576309420Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCellular Physiology and Biochemistry1,5611,561info:eu-repo/semantics/openAccess2024-08-14T17:36:41Zoai:repositorio.unesp.br:11449/175671Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-14T17:36:41Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure
title N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure
spellingShingle N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure
Reyes, David R.A. [UNESP]
Aortic stenosis
Cardiac failure
Echocardiogram
MAPK
Rat
Tissue Doppler imaging
Ventricular remodeling
title_short N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure
title_full N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure
title_fullStr N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure
title_full_unstemmed N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure
title_sort N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure
author Reyes, David R.A. [UNESP]
author_facet Reyes, David R.A. [UNESP]
Gomes, Mariana J. [UNESP]
Rosa, Camila M. [UNESP]
Pagan, Luana U. [UNESP]
Damatto, Felipe C. [UNESP]
Damatto, Ricardo L. [UNESP]
Depra, Igor [UNESP]
Campos, Dijon H.S. [UNESP]
Fernandez, Ana A.H. [UNESP]
Martinez, Paula F.
Okoshi, Katashi [UNESP]
Okoshi, Marina P. [UNESP]
author_role author
author2 Gomes, Mariana J. [UNESP]
Rosa, Camila M. [UNESP]
Pagan, Luana U. [UNESP]
Damatto, Felipe C. [UNESP]
Damatto, Ricardo L. [UNESP]
Depra, Igor [UNESP]
Campos, Dijon H.S. [UNESP]
Fernandez, Ana A.H. [UNESP]
Martinez, Paula F.
Okoshi, Katashi [UNESP]
Okoshi, Marina P. [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Campo Grande
dc.contributor.author.fl_str_mv Reyes, David R.A. [UNESP]
Gomes, Mariana J. [UNESP]
Rosa, Camila M. [UNESP]
Pagan, Luana U. [UNESP]
Damatto, Felipe C. [UNESP]
Damatto, Ricardo L. [UNESP]
Depra, Igor [UNESP]
Campos, Dijon H.S. [UNESP]
Fernandez, Ana A.H. [UNESP]
Martinez, Paula F.
Okoshi, Katashi [UNESP]
Okoshi, Marina P. [UNESP]
dc.subject.por.fl_str_mv Aortic stenosis
Cardiac failure
Echocardiogram
MAPK
Rat
Tissue Doppler imaging
Ventricular remodeling
topic Aortic stenosis
Cardiac failure
Echocardiogram
MAPK
Rat
Tissue Doppler imaging
Ventricular remodeling
description Background/Aims: To evaluate the effects of the antioxidant N-acetylcysteine (NAC) on cardiac structure and function in rats with long-term ascending aortic stenosis (AS). Methods: Four months after inducing AS, Wistar rats were assigned into the groups Sham, AS, and AS treated with NAC (AS-NAC) and followed for eight weeks. Cardiac structure and function were evaluated by echocardiogram. Myocardial antioxidant enzymes activity was measured by spectrophotometry and malondialdehyde serum concentration by HPLC. Gene expression of NADPH oxidase subunits NOX2, NOX4, p22 phox, and p47 phox was assessed by real time RT-PCR and protein expression of MAPK proteins by Western blot. Statistical analyzes were performed with Goodman and ANOVA or Mann-Whitney Results: NAC restored myocardial total glutathione (Sham 20.8±3.00; AS 12.6±2.92; AS-NAC 17.6±2.45 nmol/g tissue; p<0.05 AS vs Sham and AS-NAC). Malondialdehyde serum concentration was lower in AS-NAC and myocardial lipid hydroperoxide was higher in AS (Sham 199±48.1; AS 301±36.0; AS-NAC 181±41.3 nmol/g tissue). Glutathione peroxidase activity was lower in AS than Sham. Echocardiogram showed LV concentric hypertrophy with systolic and diastolic dysfunction before and after treatment; no differences were observed between AS-NAC and AS groups. NAC reduced p-ERK and p-JNK protein expression, attenuated myocardial fibrosis, and decreased the frequency of right ventricular hypertrophy. Conclusion: N-acetylcysteine restores myocardial total glutathione, reduces systemic and myocardial oxidative stress, improves MAPK signaling, and attenuates myocardial fibrosis in aortic stenosis rats.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-11T17:17:01Z
2018-12-11T17:17:01Z
2018-01-01
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://dx.doi.org/10.1159/000486115
Cellular Physiology and Biochemistry, v. 44, n. 6, p. 2310-2321, 2018.
1421-9778
1015-8987
http://hdl.handle.net/11449/175671
10.1159/000486115
2-s2.0-85038635123
2-s2.0-85038635123.pdf
1590971576309420
url http://dx.doi.org/10.1159/000486115
http://hdl.handle.net/11449/175671
identifier_str_mv Cellular Physiology and Biochemistry, v. 44, n. 6, p. 2310-2321, 2018.
1421-9778
1015-8987
10.1159/000486115
2-s2.0-85038635123
2-s2.0-85038635123.pdf
1590971576309420
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Cellular Physiology and Biochemistry
1,561
1,561
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 2310-2321
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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