Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse

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Autor(es): dc.contributorSão Francisco University Medical School-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.contributorThe Johns Hopkins School of Medicine-
Autor(es): dc.creatorPinheiro, Andressa Kely-
Autor(es): dc.creatorPereira, Dalila Andrade-
Autor(es): dc.creatorSantos, Jean Leandro dos-
Autor(es): dc.creatorCalmasini, Fabiano Beraldi-
Autor(es): dc.creatorAlexandre, Eduardo Costa-
Autor(es): dc.creatorReis, Leonardo Oliveira-
Autor(es): dc.creatorBurnett, Arthur L.-
Autor(es): dc.creatorCosta, Fernando Ferreira-
Autor(es): dc.creatorSilva, Fábio Henrique-
Data de aceite: dc.date.accessioned2025-08-21T21:55:06Z-
Data de disponibilização: dc.date.available2025-08-21T21:55:06Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-06-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0269310-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/240179-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/240179-
Descrição: dc.descriptionBackground 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.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionLaboratory of Multidisciplinary Research São Francisco University Medical School, Paulista SP-
Descrição: dc.descriptionState University of São Paulo (UNESP) School of Pharmaceutical Science Laboratory of Drug Discovery, SP-
Descrição: dc.descriptionDepartment of Structural and Functional Biology University of Campinas, SP-
Descrição: dc.descriptionDepartment of Pharmacology Faculty of Medical Sciences University of Campinas, SP-
Descrição: dc.descriptionUroScience Pontifical Catholic University of Campinas, SP-
Descrição: dc.descriptionThe James Buchanan Brady Urological Institute Department of Urology The Johns Hopkins School of Medicine-
Descrição: dc.descriptionHematology and Hemotherapy Center University of Campinas, SP-
Descrição: dc.descriptionState University of São Paulo (UNESP) School of Pharmaceutical Science Laboratory of Drug Discovery, SP-
Descrição: dc.descriptionFAPESP: 2014/00984-3, 2017/08122-9-
Idioma: dc.languageen-
Relação: dc.relationPLoS ONE-
???dc.source???: dc.sourceScopus-
Título: dc.titleResveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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