{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:06:18Z","timestamp":1791414378675,"version":"4.3.3"},"reference-count":46,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T00:00:00Z","timestamp":1720915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Benign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS\/BPH include alpha\u2010blockers, which relax prostatic and urethral smooth muscle and 5\u0251\u2010reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is a\u00a0cyclooxygenase\u20102\u00a0inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH\u2010associated LUTS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron\u2010sulfur protein 3\u00a0(NDUFS3) and inflammatory cells on BPH specimens from patients na\u00efve to treatment, or who were treated with celecoxib and\/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and\/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that celecoxib and\/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and\/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24766","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T06:18:53Z","timestamp":1721024333000},"page":"1309-1319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Benign prostatic hyperplasia nodules in patients treated with celecoxib and\/or finasteride have reduced levels of NADH dehydrogenase [ubiquinone] iron\u2010sulfur protein 3, a mitochondrial protein essential for efficient function of the electron transport chain"],"prefix":"10.1002","volume":"84","author":[{"given":"Teresa T.","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Urology University of Wisconsin Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5624-7614","authenticated-orcid":false,"given":"Taro","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"El\u2010Khoury","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nnamdi","family":"Ihejirika","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Paxton","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliann","family":"Jaumotte","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Dhir","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandler N.","family":"Hudson","sequence":"additional","affiliation":[{"name":"Division of Urology Southern Illinois University School of Medicine Springfield Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel B.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald B.","family":"DeFranco","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Pittsburgh Institute for Neurodegenerative Diseases University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"UPMC Hillman Cancer Center University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-1662","authenticated-orcid":false,"given":"Laura E.","family":"Pascal","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"UPMC Hillman Cancer Center University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.21037\/tau.2019.10.01"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.31"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ucl.2021.12.003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-014-1258-9"},{"issue":"10","key":"e_1_2_10_6_1","article-title":"Finasteride for benign prostatic hyperplasia","volume":"2010","author":"Tacklind J","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.03.007"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-015-1206-7"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2008.07497.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2020.09.041"},{"issue":"2","key":"e_1_2_10_11_1","first-page":"117","article-title":"Longitudinal associations between concurrent changes in phenotypic frailty and lower urinary tract symptoms among older men","volume":"12","author":"Bauer SR","year":"2023","journal-title":"J Frailty Aging"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2013.149"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.03.103"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12220"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/15579883231176667"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2008.04.069"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22668"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23324"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2012.11559.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2011.10867.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2004.08.024"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-15-0987"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.014316"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003350010160"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109002"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08839-1"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201910674"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.08.003"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e318287a90d"},{"issue":"4","key":"e_1_2_10_30_1","first-page":"234","article-title":"Increased COX\u20101 expression in benign prostate epithelial cells is triggered by mitochondrial dysfunction","volume":"10","author":"Hudson CN","year":"2022","journal-title":"Am J Clin Exp Urol"},{"key":"e_1_2_10_31_1","article-title":"Aging\u2010related mitochondrial dysfunction is associated with fibrosis in benign prostatic hyperplasia","author":"Adrian AE","year":"2023","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/09603271211053299"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2015.12.003"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1039622"},{"issue":"1","key":"e_1_2_10_35_1","first-page":"1","article-title":"BCL\u20102 and BCL\u2010XL expression are down\u2010regulated in benign prostate hyperplasia nodules and not affected by finasteride and\/or celecoxib","volume":"6","author":"Li F","year":"2018","journal-title":"Am J Clin Exp Urol"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23806"},{"issue":"1","key":"e_1_2_10_37_1","first-page":"140","article-title":"E\u2010cadherin expression is inversely correlated with aging and inflammation in the prostate","volume":"9","author":"Pascal LE","year":"2021","journal-title":"Am J Clin Exp Urol"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa212"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24611"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010716-104908"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012419-032711"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2006.09.008"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.04.008"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000002183"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01274-x"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.01.028"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00602.2015"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.24766","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T05:42:09Z","timestamp":1725946929000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.24766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,14]]},"references-count":46,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/pros.24766"],"URL":"https:\/\/doi.org\/10.1002\/pros.24766","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,14]]},"assertion":[{"value":"2024-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}