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NaBu (20\u00a0mg\/kg\/day) was administered orally to rats for 6 weeks after creation of PBOO. In vivo erectile responses, in vitro relaxation and contraction responses in cavernosal tissue were measured. Real\u2010time polymerase chain reaction (RT\u2010PCR) and Western blot were performed to determine the gene and protein expression. Inflammation, fibrosis, and localization of proteins were evaluated using histological techniques. HDAC activity and tumor necrosis factor (TNF)\u2010\u03b1 levels were measured in penile tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NaBu improved decreased intracavernosal pressure\/mean arterial pressure, nitrergic and endothelium\u2010dependent relaxation responses, and contractile responses to phenylephrine and electrical field stimulation in the PBOO group without affecting increased bladder weight. Increased endothelial nitric oxide synthase (eNOS), transforming growth factor (TGF)\u2010\u03b21, and nuclear factor kappa B (NF\u2010\u03baB) gene levels in PBOO group were ameliorated by NaBu treatment. The administration of NaBu to PBOO rats significantly increased neuronal NOS (nNOS) and decreased TGF\u2010\u03b21 protein expression. The nuclear\/cytosolic ratio of NF\u2010\u03baB demonstrated a decrease in PBOO and all treatment groups compared to control. A significant increase in the nuclear\u2010to\u2010cytoplasmic ratio of nuclear factor erythroid 2\u2010related factor 2 (Nrf2) after PBOO was reduced by the treatment. Both eNOS and inducible NOS (iNOS) protein expression, together with TNF\u2010\u03b1 levels did not differ in the penile tissue of all groups. In histological analysis, increased TGF\u2010\u03b21 protein expression and fibrosis, as well as decreased nNOS protein in PBOO, were reversed by the treatment. NaBu did not normalize moderate inflammation in obstructed rats. An increase in the HDAC activity in PBOO was significantly suppressed by NaBu.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Inhibition of the HDAC activity by NaBu in penile tissue could ameliorate fibrosis\u2010associated changes induced by PBOO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NaBu promotes recovery of erectile function, and also significantly prevents penile fibrosis and normalizes TGF\u2010\u03b21 and nNOS protein expression in a rat model of PBOO. The HDAC pathway may present a promising target to prevent ED in patients with BPH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13231","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T13:47:35Z","timestamp":1658238455000},"page":"1441-1453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sodium butyrate ameliorates erectile dysfunction through fibrosis in a rat model of partial bladder outlet obstruction"],"prefix":"10.1111","volume":"10","author":[{"given":"Ecem","family":"Kaya\u2010Sezginer","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Department of Biochemistry Ankara University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didem","family":"Yilmaz\u2010Oral","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology Cukurova University  Adana 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