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• W2044148846 abstract "No AccessJournal of UrologyInvestigative Urology1 May 2009Sesquiterpene Lactone Parthenolide Ameliorates Bladder Inflammation and Bladder Overactivity in Cyclophosphamide Induced Rat Cystitis Model by Inhibiting Nuclear Factor-κB Phosphorylationis accompanied byLearning to Control Cyclophosphamide Induced Cystitis Hiroshi Kiuchi, Tetsuya Takao, Keisuke Yamamoto, Jiro Nakayama, Yasushi Miyagawa, Akira Tsujimura, Norio Nonomura, and Akihiko Okuyama Hiroshi KiuchiHiroshi Kiuchi More articles by this author , Tetsuya TakaoTetsuya Takao More articles by this author , Keisuke YamamotoKeisuke Yamamoto More articles by this author , Jiro NakayamaJiro Nakayama More articles by this author , Yasushi MiyagawaYasushi Miyagawa More articles by this author , Akira TsujimuraAkira Tsujimura More articles by this author , Norio NonomuraNorio Nonomura More articles by this author , and Akihiko OkuyamaAkihiko Okuyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.01.015AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Cyclophosphamide (Sigma®) is associated with urological complications, including irritative voiding symptoms and hemorrhagic cystitis. Evidence suggests that tumor necrosis factor-α (R&D Systems®), interleukin-1β and cyclooxygenase-2 are directly involved in the pathogenesis of cyclophosphamide induced cystitis and these molecules depend on transcription factor NF-κB for maximal secretion. Additionally, sesquiterpene lactone parthenolide has been shown to be a potent nuclear factor-κB inhibitor. We hypothesized that enhanced nuclear factor-κB activity contributes to cyclophosphamide induced cystitis and, therefore, it may be an attractive target for preventing cyclophosphamide cystitis. We determined whether parthenolide could be used as a preventive agent for hemorrhagic cystitis and bladder overactivity. Moreover, we determined the molecular mechanisms of parthenolide on the inhibitory action of nuclear factor-κB in inflammatory human benign urothelial cells. Materials and Methods: Rats were pretreated with parthenolide or vehicle solution and administered cyclophosphamide. Histological analysis and cystometry were performed 24 hours after cyclophosphamide administration. Human urothelial cells were pretreated with parthenolide and stimulated with tumor necrosis factor-α. Western blotting and immunofluorescence were performed to determine activation of the cyclooxygenase-2 and nuclear factor-κB pathway. Results: Parthenolide pretreatment inhibited bladder inflammation as well as bladder overactivity and it was also associated with nuclear factor-κB activation in the bladder. Parthenolide dose dependently suppressed tumor necrosis factor-α induced cyclooxygenase-2 expression and prevented nuclear factor-κB phosphorylation as well as nuclear factor-κB nuclear translocation and IκBα phosphorylation/degradation. Conclusions: Nuclear factor-κB may have a crucial role in the pathogenesis of cyclophosphamide induced cystitis models. 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Google Scholar Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan© 2009 by American Urological AssociationFiguresReferencesRelatedDetailsCited ByVykhovanets E, MacLennan G, Vykhovanets O, Cherullo E, Ponsky L and Gupta S (2018) Molecular Imaging of Nuclear Factor-κB in Bladder as a Primary Regulator of Inflammatory ResponseJournal of Urology, VOL. 187, NO. 1, (330-337), Online publication date: 1-Jan-2012.Related articlesJournal of Urology16 Mar 2009Learning to Control Cyclophosphamide Induced Cystitis Volume 181Issue 5May 2009Page: 2339-2348 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordscyclophosphamideparthenolideurinary bladderNF-kappa BcystitisMetricsAuthor Information Hiroshi Kiuchi More articles by this author Tetsuya Takao More articles by this author Keisuke Yamamoto More articles by this author Jiro Nakayama More articles by this author Yasushi Miyagawa More articles by this author Akira Tsujimura More articles by this author Norio Nonomura More articles by this author Akihiko Okuyama More articles by this author Expand All Advertisement PDF DownloadLoading ..." @default.
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