Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0269310 http://hdl.handle.net/11449/240179 |
Resumo: | Background Children and adult with sickle cell disease (SCD) display priapism associated with low nitric oxide (NO) bioavailability and oxidative stress in penis. Aim This study aimed to evaluate the effects of hybrid compound RVT-FxMe, derived from resveratrol bearing a NO-donor subunit, on two murine model that display priapism phenotype, SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice. Methods Wild-type, SCD, and eNOS-/- mice were treated with RVT-FxMe (25 mg/kg/d, 2 weeks). Outcomes Hematological parameters, concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as to electrical field stimulation (EFS), were obtained in mice corpus cavernosum strips. Results Corpus cavernosum relaxations to SNP and EFS were increased in eNOS-/- group, which were normalized by RVT-FxMe treatment. SCD mice exhibited an excessive CC relaxant response induced by ACh, EFS and SNP RVT-FxMe treatment did not change the increased relaxant responses to ACh, EFS and SNP in corpus cavernosum from SCD group. Clinical translation Excess of plasma hemoglobin in SCD may interfere in pharmacological activity of NO donors compounds. Strength/Limitations While mechanistic data with promising potential is showed, the current study is not without limitations. RVT-FxMe effects in the mid- and long-term warrant complementary studies. Conclusion Treatment with RVT-FxMe reversed the enhanced NO-cGMP-mediated CC relaxations in eNOS-/- mice, but not in SCD mice; it is likely that excess of plasma hemoglobin in SCD mice act to inactivate NO before it reaches soluble guanylyl cyclase, avoiding restoration of NO bioavailability in penis. |
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Repositório Institucional da UNESP |
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spelling |
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouseBackground Children and adult with sickle cell disease (SCD) display priapism associated with low nitric oxide (NO) bioavailability and oxidative stress in penis. Aim This study aimed to evaluate the effects of hybrid compound RVT-FxMe, derived from resveratrol bearing a NO-donor subunit, on two murine model that display priapism phenotype, SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice. Methods Wild-type, SCD, and eNOS-/- mice were treated with RVT-FxMe (25 mg/kg/d, 2 weeks). Outcomes Hematological parameters, concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as to electrical field stimulation (EFS), were obtained in mice corpus cavernosum strips. Results Corpus cavernosum relaxations to SNP and EFS were increased in eNOS-/- group, which were normalized by RVT-FxMe treatment. SCD mice exhibited an excessive CC relaxant response induced by ACh, EFS and SNP RVT-FxMe treatment did not change the increased relaxant responses to ACh, EFS and SNP in corpus cavernosum from SCD group. Clinical translation Excess of plasma hemoglobin in SCD may interfere in pharmacological activity of NO donors compounds. Strength/Limitations While mechanistic data with promising potential is showed, the current study is not without limitations. RVT-FxMe effects in the mid- and long-term warrant complementary studies. Conclusion Treatment with RVT-FxMe reversed the enhanced NO-cGMP-mediated CC relaxations in eNOS-/- mice, but not in SCD mice; it is likely that excess of plasma hemoglobin in SCD mice act to inactivate NO before it reaches soluble guanylyl cyclase, avoiding restoration of NO bioavailability in penis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Laboratory of Multidisciplinary Research São Francisco University Medical School, Paulista SPState University of São Paulo (UNESP) School of Pharmaceutical Science Laboratory of Drug Discovery, SPDepartment of Structural and Functional Biology University of Campinas, SPDepartment of Pharmacology Faculty of Medical Sciences University of Campinas, SPUroScience Pontifical Catholic University of Campinas, SPThe James Buchanan Brady Urological Institute Department of Urology The Johns Hopkins School of MedicineHematology and Hemotherapy Center University of Campinas, SPState University of São Paulo (UNESP) School of Pharmaceutical Science Laboratory of Drug Discovery, SPFAPESP: 2014/00984-3, 2017/08122-9São Francisco University Medical SchoolUniversidade Estadual Paulista (UNESP)Universidade Estadual de Campinas (UNICAMP)The Johns Hopkins School of MedicinePinheiro, Andressa KelyPereira, Dalila AndradeSantos, Jean Leandro dos [UNESP]Calmasini, Fabiano BeraldiAlexandre, Eduardo CostaReis, Leonardo OliveiraBurnett, Arthur L.Costa, Fernando FerreiraSilva, Fábio Henrique2023-03-01T20:05:02Z2023-03-01T20:05:02Z2022-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1371/journal.pone.0269310PLoS ONE, v. 17, n. 6 June, 2022.1932-6203http://hdl.handle.net/11449/24017910.1371/journal.pone.02693102-s2.0-85131236392Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLoS ONEinfo:eu-repo/semantics/openAccess2023-03-01T20:05:02Zoai:repositorio.unesp.br:11449/240179Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-03-01T20:05:02Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse |
title |
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse |
spellingShingle |
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse Pinheiro, Andressa Kely |
title_short |
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse |
title_full |
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse |
title_fullStr |
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse |
title_full_unstemmed |
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse |
title_sort |
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse |
author |
Pinheiro, Andressa Kely |
author_facet |
Pinheiro, Andressa Kely Pereira, Dalila Andrade Santos, Jean Leandro dos [UNESP] Calmasini, Fabiano Beraldi Alexandre, Eduardo Costa Reis, Leonardo Oliveira Burnett, Arthur L. Costa, Fernando Ferreira Silva, Fábio Henrique |
author_role |
author |
author2 |
Pereira, Dalila Andrade Santos, Jean Leandro dos [UNESP] Calmasini, Fabiano Beraldi Alexandre, Eduardo Costa Reis, Leonardo Oliveira Burnett, Arthur L. Costa, Fernando Ferreira Silva, Fábio Henrique |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
São Francisco University Medical School Universidade Estadual Paulista (UNESP) Universidade Estadual de Campinas (UNICAMP) The Johns Hopkins School of Medicine |
dc.contributor.author.fl_str_mv |
Pinheiro, Andressa Kely Pereira, Dalila Andrade Santos, Jean Leandro dos [UNESP] Calmasini, Fabiano Beraldi Alexandre, Eduardo Costa Reis, Leonardo Oliveira Burnett, Arthur L. Costa, Fernando Ferreira Silva, Fábio Henrique |
description |
Background Children and adult with sickle cell disease (SCD) display priapism associated with low nitric oxide (NO) bioavailability and oxidative stress in penis. Aim This study aimed to evaluate the effects of hybrid compound RVT-FxMe, derived from resveratrol bearing a NO-donor subunit, on two murine model that display priapism phenotype, SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice. Methods Wild-type, SCD, and eNOS-/- mice were treated with RVT-FxMe (25 mg/kg/d, 2 weeks). Outcomes Hematological parameters, concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as to electrical field stimulation (EFS), were obtained in mice corpus cavernosum strips. Results Corpus cavernosum relaxations to SNP and EFS were increased in eNOS-/- group, which were normalized by RVT-FxMe treatment. SCD mice exhibited an excessive CC relaxant response induced by ACh, EFS and SNP RVT-FxMe treatment did not change the increased relaxant responses to ACh, EFS and SNP in corpus cavernosum from SCD group. Clinical translation Excess of plasma hemoglobin in SCD may interfere in pharmacological activity of NO donors compounds. Strength/Limitations While mechanistic data with promising potential is showed, the current study is not without limitations. RVT-FxMe effects in the mid- and long-term warrant complementary studies. Conclusion Treatment with RVT-FxMe reversed the enhanced NO-cGMP-mediated CC relaxations in eNOS-/- mice, but not in SCD mice; it is likely that excess of plasma hemoglobin in SCD mice act to inactivate NO before it reaches soluble guanylyl cyclase, avoiding restoration of NO bioavailability in penis. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-06-01 2023-03-01T20:05:02Z 2023-03-01T20:05:02Z |
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/10.1371/journal.pone.0269310 PLoS ONE, v. 17, n. 6 June, 2022. 1932-6203 http://hdl.handle.net/11449/240179 10.1371/journal.pone.0269310 2-s2.0-85131236392 |
url |
http://dx.doi.org/10.1371/journal.pone.0269310 http://hdl.handle.net/11449/240179 |
identifier_str_mv |
PLoS ONE, v. 17, n. 6 June, 2022. 1932-6203 10.1371/journal.pone.0269310 2-s2.0-85131236392 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS ONE |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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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1803650174646484992 |