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Int. J. Mol. Sci. 2017, 18(1), 117; doi:10.3390/ijms18010117

Ketamine Analog Methoxetamine Induced Inflammation and Dysfunction of Bladder in Rats

1
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
2
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Irmgard Tegeder
Received: 22 October 2016 / Revised: 26 December 2016 / Accepted: 28 December 2016 / Published: 18 January 2017
(This article belongs to the Special Issue Pain and Inflammation)
View Full-Text   |   Download PDF [14421 KB, uploaded 18 January 2017]   |  

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. View Full-Text
Keywords: methoxetamine; bladder dysfunction; cystitis; cytokines; ketamine methoxetamine; bladder dysfunction; cystitis; cytokines; ketamine
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Wang, Q.; Wu, Q.; Wang, J.; Chen, Y.; Zhang, G.; Chen, J.; Zhao, J.; Wu, P. Ketamine Analog Methoxetamine Induced Inflammation and Dysfunction of Bladder in Rats. Int. J. Mol. Sci. 2017, 18, 117.

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