Intravesical IR-780 instillation prevents radiation cystitis by protecting urothelial integrity

作者全名："Li, Jinjin; Shen, Chongxing; Qiu, Heping; Wang, Jianwu; Yue, Xiaofeng; Dai, Linyong; Huang, Yuandi; Li, Tong; Fang, Qiang; Zhi, Yi; Shi, Chunmeng; Li, Weibing"

作者地址："[Li, Jinjin; Shen, Chongxing; Qiu, Heping; Wang, Jianwu; Yue, Xiaofeng; Dai, Linyong; Huang, Yuandi; Li, Tong; Fang, Qiang; Zhi, Yi; Li, Weibing] Chongqing Med Univ, Affiliated Hosp 3, Dept Urol, 1 Shuanghu Branch Rd,Huixing St, Chongqing 401120, Peoples R China; [Shi, Chunmeng] Army Med Univ, Inst Rocket Force Med, State Key Lab Trauma Burns & Combined Injury, Chongqing, Peoples R China"

通信作者："Zhi, Y; Li, WB (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Urol, 1 Shuanghu Branch Rd,Huixing St, Chongqing 401120, Peoples R China.; Shi, CM (通讯作者)，Third Mil Med Univ, Inst Rocket Force Med, State Key Lab Trauma Burns & Combined Injury, Chongqing 400038, Peoples R China."

来源：NEUROUROLOGY AND URODYNAMICS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000865056100001

JCR分区：Q3

影响因子：2

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：IR-780; mitochondria; radiation cystitis; radiotherapy; urothelium

摘要："Purpose To explore an efficient preventive strategy for radiation cystitis. Methods We instilled IR-780 into the bladders of rats 1 h before bladder irradiation, and its bio-distribution was observed at different times. Bladders were then examined for pathogenic alterations and inflammation levels by day 3 and week 12 postirradiation, and the functional characteristics of the bladder were tested via cystometry by week 12. Human uroepithelial sv-huc-1 cells were used to determine the effect of IR-780 on cell viability, regardless of irradiation. We measured the intracellular levels of oxidative stress, DNA damage, apoptosis proportion, and the expression of antioxidant proteases and apoptotic caspases in IR-780 pretreated cells after radiation. Results IR-780 is localized in the urothelium after intravesical instillation in vivo. Ionizing radiation could induce acute impairment of the bladder urothelium and inflammation in the bladder on day 3. Fibrosis of the irradiated bladder progressed and eventually affected voiding function at 12 weeks. Treatment with IR-780 before irradiation ameliorated these changes. In vitro, IR-780 protected against cell viability and apoptosis of sv-huc-1 cells after irradiation. Additionally, IR-780 may assist in eliminating reactive oxygen species and repairing irradiation-induced DNA damage. Conclusion Our data indicate that IR-780 can be used before irradiation to prevent acute urinary mucosal injury and late bladder dysfunction. Moreover, early urothelial impairment plays a significant role in radiation cystitis development."

基金机构：National Natural Science Foundation of China; Intramural Research Project Grant

基金资助正文：National Natural Science Foundation of China; Intramural Research Project Grant