Ketamine Analog Methoxetamine Induced Inflammation and Dysfunction of Bladder in Rats
Qiang Wang, Qinghui Wu, Junpeng Wang, Yang Chen, Guihao Zhang, Jiawei Chen, Jie Zhao, Peng Wu
International Journal of Molecular Sciences January 18, 2017 DOI: 10.3390/ijms18010117 (opens in new tab)
Summary
AI-generated from the abstractLong-term methoxetamine, a ketamine analog used recreationally, causes bladder dysfunction and inflammation in rats. Female rats injected daily with 30 mg/kg methoxetamine or ketamine for 4 or 12 weeks showed increased urination frequency, damaged bladder lining, inflammatory cell infiltration, and fibrosis. Treated rats had elevated levels of pro-inflammatory cytokines and markers of fibrosis. Methoxetamine also directly damaged human urothelial cells and increased inflammatory signals. The findings suggest methoxetamine's bladder effects resemble ketamine-induced cystitis.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Female Sprague-Dawley rats and human urothelial cells |
| Interventions | Methoxetamine Ketamine |
| Dose | 30 mg/kg |
| Duration | 4 or 12 weeks |
| Key finding | Long-term methoxetamine treatment induces bladder dysfunction and inflammation in rats, similar to ketamine-induced cystitis. |
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.