NDLI: Long-term ketamine abuse induces cystitis in rats by impairing the bladder epithelial barrier

Content Provider	Springer Nature Link
Author	Gu, Di Huang, Jun Yin, Youle Shan, Zhengfei Zheng, Shaobin Wu, Peng
Copyright Year	2014
Abstract	Long-term ketamine abuse is known to affect the lower urinary tract and produce symptoms of cystitis. However, the pathophysiology and causative mechanism of the changes in bladder function remain unclear. The present study aimed to investigate the existence of ketamine-induced cystitis in a rat model and characterize the underlining mechanisms. Rats were assigned to blank control, normal saline (NS), low-dose ketamine (LK, 5 mg/kg), and high-dose ketamine (HK, 50 mg/kg) groups. The two experimental groups received ketamine hydrochloride daily for 16 weeks. All rats were housed individually for assessment of urinary frequency and urine volume. Urinary biomarkers were measured at different time points. Rat bladders were excised for histopathology, immunohistochemistry, and western blot analysis. Ketamine-treated rats had increased urinary frequency compared to NS-treated rats at Week 16. Urinary nitric oxide and antiproliferative factor levels were increased in ketamine-treated rats within the first 30 h after administration. After long-term ketamine administration, urinary glycoprotein GP51 and potassium levels were decreased in the HK and LK groups compared to the NS group. Ketamine-treated rats showed thickened bladder epithelial layer, increased expression of inducible nitric oxide synthase and occludin, and decreased expression of zonula occludens-1 in the bladder wall. Ketamine, or its urinary metabolites, disrupted the proliferation of bladder epithelial cells, resulting in defected bladder epithelial barrier. Subsequent leakage of urinary potassium causes a stress response in the bladder and provokes cystitis.
Starting Page	7313
Ending Page	7322
Page Count	10
File Format	PDF
ISSN	03014851
Journal	Molecular Biology Reports
Volume Number	41
Issue Number	11
e-ISSN	15734978
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-08-05
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Ketamine Cystitis Bladder epithelial barrier Urinary frequency Rats Animal Biochemistry Animal Anatomy / Morphology / Histology
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Molecular Biology

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