{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T05:09:17Z","timestamp":1774156157856,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation","award":["2017\/08122-9"],"award-info":[{"award-number":["2017\/08122-9"]}]},{"name":"S\u00e3o Paulo Research Foundation","award":["2019\/18886-1"],"award-info":[{"award-number":["2019\/18886-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bladder dysfunction, particularly overactive bladder (OAB), is increasingly recognized as a clinical concern in patients with sickle cell disease (SCD), yet its pathophysiological mechanisms remain poorly understood. This study investigated the relationship between oxidative stress, inflammation, and bladder dysfunction in the Townes transgenic SCD mouse model. Cystometric analysis revealed that SCD mice exhibit an OAB phenotype, characterized by increased frequencies of voiding and non-voiding contractions and reduced bladder compliance. In vitro functional assays demonstrated detrusor hypocontractility in SCD mice, associated with a significant reduction in carbachol- and EFS-induced contractions and downregulation of muscarinic M3 receptor expression. Purinergic signaling and calcium-dependent contractility remained preserved. Molecular analyses showed increased mRNA expression of NOX-2 and IL-1\u03b2, and elevated protein levels of 3-nitrotyrosine and myeloperoxidase (MPO) activity, indicating redox imbalance and chronic inflammation in bladder tissue. Together, these changes suggest that oxidative and nitrosative stress, combined with inflammation, contribute to bladder remodeling and dysfunction in SCD. This is the first study to characterize bladder alterations in Townes SCD mice, establishing this model as a valuable tool for investigating lower urinary tract complications in SCD. Our findings provide mechanistic insight into the genitourinary manifestations of SCD and identify redox and inflammatory pathways as potential therapeutic targets for bladder dysfunction in affected individuals.<\/jats:p>","DOI":"10.3390\/ijms26199776","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T08:22:08Z","timestamp":1759911728000},"page":"9776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bladder Dysfunction in Sickle Cell Disease Is Associated with Inflammation and Oxidative Stress"],"prefix":"10.3390","volume":"26","author":[{"given":"Dalila Andrade","family":"Pereira","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, S\u00e3o Francisco University Medical School, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7790-2550","authenticated-orcid":false,"given":"Fabiano Beraldi","family":"Calmasini","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Paulista School of Medicine, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04044-010, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammyris Helena Rebecchi","family":"Silveira","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, S\u00e3o Francisco University Medical School, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danillo Andrade","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, S\u00e3o Francisco University Medical School, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2226-2530","authenticated-orcid":false,"given":"Mariana G.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, S\u00e3o Francisco University Medical School, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Ferreira","family":"Costa","sequence":"additional","affiliation":[{"name":"Hematology and Hemotherapy Center, University of Campinas, Campinas 13000-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e1bio Henrique","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, S\u00e3o Francisco University Medical School, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18010","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle Cell Disease","volume":"4","author":"Kato","year":"2018","journal-title":"Nat. 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