PD23-08 N-ACETYLCYSTEINE AMELIORATES HIGH GLUCOSE-INDUCED BLADDER DYSFUNCTION ASSOCIATED WITH METABOLIC SYNDROMES BY MEDIATING MITOCHONDRIAL FUNCTION AND THE ROS/NLRP3/NF-κB SIGNALING PATHWAYS

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD23-08 N-ACETYLCYSTEINE AMELIORATES HIGH GLUCOSE-INDUCED BLADDER DYSFUNCTION ASSOCIATED WITH METABOLIC SYNDROMES BY MEDIATING MITOCHONDRIAL FUNCTION AND THE ROS/NLRP3/NF-κB SIGNALING PATHWAYS Qiqi He, Junsheng Bao, Panfeng Shang, Li Yang, Zhiping Wang, and Sanjay Gupta Qiqi HeQiqi He More articles by this author , Junsheng BaoJunsheng Bao More articles by this author , Panfeng ShangPanfeng Shang More articles by this author , Li YangLi Yang More articles by this author , Zhiping WangZhiping Wang More articles by this author , and Sanjay GuptaSanjay Gupta More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003296.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We previously demonstrated that metabolic syndromes contribute to bladder dysfunction by altering the phenotype of bladder smooth muscles. We conducted this study to further examine the potential molecular mechanisms of metabolic syndromes (MS)-mediated bladder dysfunctions to facilitate diagnosis and therapeutic interventions. METHODS: In vitro, bladder muscle cells from C57BL/6N mice were cultured and divided into the control group, HG (45 MM) group, HG (45 MM)+NAC (5 MM) group, and HOS (50 MM) group. Oxidative stress, inflammation and fibrosis levels in BSMCs were observed by qRT‒PCR and Western blot analysis. Functional and morphological changes in mitochondria were examined. In vivo, forty SD rats (6 wks of age) were divided into four groups and bred until twenty weeks: control (CON), High Fat Diet (HFD), HFD+300 mg/kg/d NAC (HFD+LNAC), and HFD+900 mg/kg/d NAC (HFD+HNAC)}. At the end of the 20 weeks, blood and bladder smooth muscle samples were collected, and OS and contractile levels were examined. RESULTS: In vitro, high glucose significantly enhanced oxidative stress, inflammation and fibrosis in BSMCs. Moreover, the increase in cytokine expression was accompanied by enhanced NLRP3 expression and the phosphorylation of NF-κB. However, N-acetylcysteine had an inhibitory effect on the expression of ROS/NLRP3/NF-κB and the dissolution of mitochondria in HG-treated BSMCs. In vivo, compared to those in the control group, the mean contractility and frequency of bladder smooth muscles in the HFD group was significantly decreased (p<0.01). The mean contractility in the LNAC+HFD group was significantly higher than that in the HFD group (p<0.01). Interestingly, the HNAC+HFD group did not show any recovery in muscle contractility but exhibited significantly reduced bladder contractile frequency (p<0.01). CONCLUSIONS: Our findings indicated that high glucose-induced oxidative stress, inflammation and fibrosis are mainly mediated by the ROS/NLRP3/NF-κB signaling pathways and mitochondrial changes in BSMCs. NAC ameliorated these changes by blocking the ROS/NLRP3/NF-κB signaling pathways and protecting mitochondrial function and morphology. Source of Funding: National Natural Science Foundation of China ( 81800671), Cuiyin Talent Program (CY2021-MS-A02) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e674 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Qiqi He More articles by this author Junsheng Bao More articles by this author Panfeng Shang More articles by this author Li Yang More articles by this author Zhiping Wang More articles by this author Sanjay Gupta More articles by this author Expand All Advertisement PDF downloadLoading ...