title: Biological effect of ketamine in urothelial cell lines and global gene expression analysis in the bladders of ketamine‑injected mice.
abstract: Ketamine is used clinically for anesthesia but is also abused as a recreational drug. Previously, it has been established that ketamine‑induced bladder interstitial cystitis is a common syndrome in ketamine‑abusing individuals. As the mechanisms underlying ketamine‑induced cystitis have yet to be revealed, the present study investigated the effect of ketamine on human urothelial cell lines and utilized a ketamine‑injected mouse model to identify ketamine‑induced changes in gene expression in mice bladders. In the in vitro bladder cell line assay, ketamine induced cytotoxicity in a dose‑ and time‑dependent manner. Ketamine arrested the cells in G1 phase and increased the sub‑G1 population, and also increased the barrier permeability of these cell lines. In the ketamine‑injected mouse model, ketamine did not change the body weight and bladder histology of the animals at the dose of 30 mg/kg/day for 60 days. Global gene expression analysis of the animals' bladders following data screening identified ten upregulated genes and 36 downregulated genes induced by ketamine. A total of 52% of keratin family genes were downregulated, particularly keratin 6a, 13 and 14, which was confirmed by polymerase chain reaction analysis. Keratin 14 protein, one of the 36 ketamine‑induced downregulated genes, was also reduced in the ketamine‑treated mouse bladder, as determined by immunohistochemical analysis. This suggested that cytotoxicity and keratin gene downregulation may have a critical role in ketamine‑induced cystitis.
authors.affiliation: Department of Urology, Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C.
authors.forename: Cheng-Huang
authors.initials: CH
authors.lastname: Shen
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan, R.O.C.
authors.forename: Shou-Tsung
authors.initials: ST
authors.lastname: Wang
authors.affiliation: Department of Medical Research, Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C.
authors.forename: Ying-Ray
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan, R.O.C.
authors.forename: Shiau-Yuan
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan, R.O.C.
authors.forename: Yi-Zhen
authors.initials: YZ
authors.lastname: Li
authors.affiliation: Department of Pathology, Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C.
authors.forename: Jiann-Der
authors.initials: JD
authors.lastname: Wu
authors.affiliation: Department of Pathology, Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan, R.O.C.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Liu
mesh_terms: D000700:Analgesics / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010539:Permeability / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000700:Analgesics; D007633:Keratins; D007649:Ketamine