Biological effect of ketamine in urothelial cell lines and global gene expression analysis in the bladders of ketamine‑injected mice

Shen,Cheng‑Huang; Wang,Shou‑Tsung; Lee,Ying‑Ray; Liu,Shiau‑Yuan; Li,Yi‑Zhen; Wu,Jiann‑Der; Chen,Yi‑Ju; Liu,Yi‑Wen

doi:10.3892/mmr.2014.2823

February-2015 Volume 11 Issue 2

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February-2015 Volume 11 Issue 2

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Article Open Access

Biological effect of ketamine in urothelial cell lines and global gene expression analysis in the bladders of ketamine‑injected mice

Authors:
- Cheng‑Huang Shen
- Shou‑Tsung Wang
- Ying‑Ray Lee
- Shiau‑Yuan Liu
- Yi‑Zhen Li
- Jiann‑Der Wu
- Yi‑Ju Chen
- Yi‑Wen Liu
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Affiliations: Department of Urology, Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C., Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan, R.O.C., Department of Medical Research, Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C., Department of Pathology, Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C.

Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 887-895
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Published online on: October 30, 2014

https://doi.org/10.3892/mmr.2014.2823
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Biological effect of ketamine in urothelial cell lines and global gene expression analysis in the bladders of ketamine‑injected mice

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