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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Bibliographic Details
Published in:Toxics (Basel) 2021-06, Vol.9 (7), p.154
Main Authors: Yeh, Chung-Hsin, Chen, Bo-He, Tseng, Xiao-Wen, Liao, Chun-Hou, Tsai, Wei-Kung, Chiang, Han-Sun, Wu, Yi-No
Format: Article
Language:English
Subjects:
Bladder
bladder dysfunction
Catheters
Collagen
Compliance
Cystitis
Deposition
Functional testing
Glycosaminoglycans
intravesical instillation
Ketamine
ketamine cystitis
Metabolism
Metabolites
Muscles
norketamine
Pathogenesis
Polyethylene
Smooth muscle
Statistical analysis
Urination
Urine
Urogenital system
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Summary: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.
ISSN:2305-6304
2305-6304
DOI:10.3390/toxics9070154