title: Ketamine Analog Methoxetamine Induced Inflammation and Dysfunction of Bladder in Rats.
abstract: The novel synthetic psychoactive ketamine analog methoxetamine is reportedly being used for recreational purposes. As ketamine use can result in urinary dysfunction, we conducted the present study to investigate how methoxetamine affects the bladder. A cystometry investigation showed that female Sprague-Dawley rats experienced increased micturition frequency bladder dysfunction after receiving a daily intraperitoneal injection of 30 mg/kg methoxetamine or ketamine for periods of 4 or 12 weeks. Histologic examinations of rat bladder tissue revealed damaged urothelium barriers, as well as evidence of inflammatory cell infiltration and matrix deposition. The drug-treated rats showed significantly upregulated levels of pro-inflammatory cytokines such as IL-1β, IL-6, CCL-2, CXCL-1, CXCL-10, NGF, and COX-2. In addition, interstitial fibrosis was confirmed by increased levels of collagen I, collagen III, fibronectin and TGF-β. Besides direct toxic effect on human urothelial cells, methoxetaminealso induced the upregulation related cytokines. Our results indicate that long term methoxetamine treatment can induce bladder dysfunction and inflammation in rats. Methoxetamine was confirmed to produce direct toxic and pro-inflammatory effects on human urothelial cells. Methoxetamine-associated bladder impairment may be similar to ketamine-induced cystitis.
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. doctorwangqiang@gmail.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. doctor_wqh@126.com.
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. wangjunpeng1990@126.com.
authors.forename: Junpeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. cyhm28@sina.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. jyzhanggh@163.com.
authors.forename: Guihao
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. miwaicjw@163.com.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. zhaojie_0412@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. doctorwupeng@gmail.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003512:Cyclohexanones / Q000633:toxicity*; D003514:Cyclohexylamines / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007649:Ketamine / Q000031:analogs & derivatives*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
chemical_list: D018925:Chemokines; D003512:Cyclohexanones; D003514:Cyclohexylamines; D018836:Inflammation Mediators; D007649:Ketamine; C569113:2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone
keywords: bladder dysfunction; cystitis; cytokines; ketamine; methoxetamine