Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in Rats

This study aimed to determine the mechanism of ketamine-induced cystitis without metabolism. A total of 24 adult male Sprague-Dawley rats were separated into control, ketamine, and norketamine groups. To induce cystitis, rats in the ketamine and norketamine groups were treated with intravesical inst...

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Main Authors: Chung-Hsin Yeh, Bo-He Chen, Xiao-Wen Tseng, Chun-Hou Liao, Wei-Kung Tsai, Han-Sun Chiang, Yi-No Wu
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/9/7/154
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author Chung-Hsin Yeh
Bo-He Chen
Xiao-Wen Tseng
Chun-Hou Liao
Wei-Kung Tsai
Han-Sun Chiang
Yi-No Wu
author_facet Chung-Hsin Yeh
Bo-He Chen
Xiao-Wen Tseng
Chun-Hou Liao
Wei-Kung Tsai
Han-Sun Chiang
Yi-No Wu
author_sort Chung-Hsin Yeh
collection DOAJ
description This study aimed to determine the mechanism of ketamine-induced cystitis without metabolism. A total of 24 adult male Sprague-Dawley rats were separated into control, ketamine, and norketamine groups. To induce cystitis, rats in the ketamine and norketamine groups were treated with intravesical instillation of ketamine and norketamine by mini-osmotic pump, which was placed in subcutaneous space, daily for 24 h for 4 weeks. After 4 weeks, all rats were subjected to bladder functional tests. The bladders were collected for histological and pathological evaluation. Compared to control, ketamine treatment demonstrated an increase in the bladder weight, high bladder/body coefficient, contractive pressure, voiding volume, collagen deposition, reduced smooth muscle content, damaged glycosaminoglycan layer, and low bladder compliance. Compared to ketamine, norketamine treatment showed more severe collagen deposition, smooth muscle loss, damaged glycosaminoglycan layer, and increased residual urine. Intravesical administration of ketamine and norketamine induced cystitis with different urodynamic characteristics. Norketamine treatment caused more severe bladder dysfunction than ketamine treatment. Direct treatment of the bladder with norketamine induced symptoms more consistent with those of bladder outlet obstruction than ketamine cystitis. Detailed studies of cellular mechanisms are required to determine the pathogenesis of ketamine cystitis.
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spelling doaj.art-a979d638f2b0463d904a642a6ddcd5b82023-11-22T02:26:50ZengMDPI AGToxics2305-63042021-06-019715410.3390/toxics9070154Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in RatsChung-Hsin Yeh0Bo-He Chen1Xiao-Wen Tseng2Chun-Hou Liao3Wei-Kung Tsai4Han-Sun Chiang5Yi-No Wu6School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, TaiwanProgram in Pharmaceutical Biotechnology, College of Medicine, Fu Jen Catholic University, New Taipei City 242, TaiwanSchool of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, TaiwanDepartment of Urology, Mackay Memorial Hospital, Taipei City 104, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, TaiwanSchool of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, TaiwanThis study aimed to determine the mechanism of ketamine-induced cystitis without metabolism. A total of 24 adult male Sprague-Dawley rats were separated into control, ketamine, and norketamine groups. To induce cystitis, rats in the ketamine and norketamine groups were treated with intravesical instillation of ketamine and norketamine by mini-osmotic pump, which was placed in subcutaneous space, daily for 24 h for 4 weeks. After 4 weeks, all rats were subjected to bladder functional tests. The bladders were collected for histological and pathological evaluation. Compared to control, ketamine treatment demonstrated an increase in the bladder weight, high bladder/body coefficient, contractive pressure, voiding volume, collagen deposition, reduced smooth muscle content, damaged glycosaminoglycan layer, and low bladder compliance. Compared to ketamine, norketamine treatment showed more severe collagen deposition, smooth muscle loss, damaged glycosaminoglycan layer, and increased residual urine. Intravesical administration of ketamine and norketamine induced cystitis with different urodynamic characteristics. Norketamine treatment caused more severe bladder dysfunction than ketamine treatment. Direct treatment of the bladder with norketamine induced symptoms more consistent with those of bladder outlet obstruction than ketamine cystitis. Detailed studies of cellular mechanisms are required to determine the pathogenesis of ketamine cystitis.https://www.mdpi.com/2305-6304/9/7/154intravesical instillationketamine cystitisnorketaminebladder dysfunction
spellingShingle Chung-Hsin Yeh
Bo-He Chen
Xiao-Wen Tseng
Chun-Hou Liao
Wei-Kung Tsai
Han-Sun Chiang
Yi-No Wu
Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in Rats
Toxics
intravesical instillation
ketamine cystitis
norketamine
bladder dysfunction
title Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in Rats
title_full Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in Rats
title_fullStr Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in Rats
title_full_unstemmed Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in Rats
title_short Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in Rats
title_sort intravesical instillation of norketamine a ketamine metabolite and induced bladder functional changes in rats
topic intravesical instillation
ketamine cystitis
norketamine
bladder dysfunction
url https://www.mdpi.com/2305-6304/9/7/154
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