N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats during Transition from Compensated Left Ventricular Hypertrophy to Heart Failure
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , |
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. |
id |
UNSP_dc8f570f52ba02688ae71a20cfeb7c0f |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/175671 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
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 |
|
_version_ |
1808128196199055360 |