{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:04:20Z","timestamp":1780524260403,"version":"3.54.1"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/08122-9"],"award-info":[{"award-number":["2017\/08122-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2012\/50359-2"],"award-info":[{"award-number":["2012\/50359-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Children and adult with sickle cell disease (SCD) display priapism associated with low nitric oxide (NO) bioavailability and oxidative stress in penis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Aim<\/jats:title>\n<jats:p>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<jats:sup>-\/-<\/jats:sup>) mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Wild-type, SCD, and eNOS<jats:sup>-\/-<\/jats:sup> mice were treated with RVT-FxMe (25 mg\/kg\/d, 2 weeks).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Outcomes<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Results<\/jats:title>\n<jats:p>Corpus cavernosum relaxations to SNP and EFS were increased in eNOS<jats:sup>-\/-<\/jats:sup> 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec006\">\n<jats:title>Clinical translation<\/jats:title>\n<jats:p>Excess of plasma hemoglobin in SCD may interfere in pharmacological activity of NO donors compounds.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec007\">\n<jats:title>Strength\/Limitations<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec008\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Treatment with RVT-FxMe reversed the enhanced NO-cGMP-mediated CC relaxations in eNOS<jats:sup>-\/-<\/jats:sup> 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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0269310","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T17:36:51Z","timestamp":1654191411000},"page":"e0269310","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse"],"prefix":"10.1371","volume":"17","author":[{"given":"Andressa Kely","family":"Pinheiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila Andrade","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Leandro","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiano Beraldi","family":"Calmasini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Costa","family":"Alexandre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Oliveira","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur L.","family":"Burnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Ferreira","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3374-5570","authenticated-orcid":true,"given":"F\u00e1bio Henrique","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"pone.0269310.ref001","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1524-6175.2006.06026.x","article-title":"The role of nitric oxide in erectile dysfunction: implications for medical therapy","volume":"8","author":"AL Burnett","year":"2006","journal-title":"J Clin Hypertens Greenwich Conn"},{"key":"pone.0269310.ref002","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1124\/pr.111.004515","article-title":"Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction.","volume":"63","author":"K-E 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