A Novel Mouse Model of Chronic Inflammatory and Overactive Bladder by a Single Intravesical Injection of Hydrogen Peroxide

Journal of Pharmacological Sciences

Takashi Homan¹  Shuji Kaneko¹  Tatsuya Oyama²  Hisashi Shirakawa¹  Koji Dogishi¹  Takayuki Nakagawa¹  Tetsunori Tsuzuki¹ 

[1] Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan;Discovery Research Laboratories, Nippon Shinyaku Co., Ltd., Japan

关键词: chronic cystitis;    hydrogen peroxide;    interstitial cystitis;    overactive bladder;    long-lasting;   

DOI  :  10.1254/jphs.12265FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(58)Cited-By(3)Supplementary materials(1)There is so far no generally accepted animal model of chronic cystitis by which potential therapies can be evaluated. In this study, we aimed to establish a new mouse model of cystitis based on the proinflammatory effects of reactive oxygen species. A single intravesical injection of 1.5% hydrogen peroxide (H2O2) significantly increased the numbers of voids by 1 day after injection in female mice, which lasted up to 7 days. The H2O2 injection rapidly increased the bladder weight by 3 h in parallel with the histological damage and hyperpermeability of urothelial barrier. Although the urothelial dysfunction was recovered to normal by 7 days, increase in bladder weight, edematous thickening of the submucosa, and vascular hyperpermeability were apparent even 7 days after injection. During the time course, massive infiltration of neutrophils and increased expression of inflammatory cytokines were observed in the bladder. An intraperitoneal administration of oxybutynin, amitriptyline, indomethacin, or morphine attenuated the H2O2-induced frequent urination. These findings suggest that an intravesical injection of H2O2 induces relatively long-lasting inflammatory and overactive bladder, compared with existing cystitis models. The intravesical H2O2 injection model may be a simple and useful tool in the pathological study and drug discovery for chronic cystitis.

【 授权许可】

Unknown