Yen-Ta Chen1,2, Chih-Chao Yang3, Pei-Hsun Sung4,2, Kun-Chen Lin5, John Y Chiang6,7, Chi-Ruei Huang4,2, Kuan-Hui Huang8, Fei-Chi Chuang8, Yi-Ching Chu4,2, Eng-Yen Huang9,10, Hon-Kan Yip4,2,11,12,13. 1. Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University Kaohsiung, Taiwan. 2. Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital Kaohsiung, Taiwan. 3. Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University Kaohsiung, Taiwan. 4. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan. 5. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan. 6. Department of Computer Science and Engineering, National Sun Yat-sen University Kaohsiung, Taiwan. 7. Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University Kaohsiung, Taiwan. 8. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University Kaohsiung, Taiwan. 9. Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University Kaohsiung, Taiwan. 10. School of Traditional Chinese Medicine, Chang Gung University College of Medicine Taoyuan, Taiwan. 11. Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital Kaohsiung, Taiwan. 12. Department of Medical Research, China Medical University Hospital, China Medical University Taichung, Taiwan. 13. Department of Nursing, Asia University Taichung, Taiwan.
Abstract
BACKGROUND: This study tested the long-term effect of extracorporeal shock wave (ECSW) therapy on ameliorating radiotherapy-induced chronic cystitis (CC) in rat. METHODS AND RESULTS: Adult-female SD rats (n = 24) were equally categorized into group 1 (normal control), group 2 (CC induced by radiotherapy with 450 cGy twice with a four-hour interval to the urinary bladder), group 3 [CC with ECSW treatment (0.1 mJ/mm2/120 impulses once every 3 days after radiotherapy)]. Bladder specimens were harvested by day 60 after radiotherapy. By day 60, the degree of detrusor contraction was significantly reduced in group 2 than groups 1 and 3, and significantly reduced in group 3 than in group 1 (P < 0.0001). Number of WBC, occulted blood and bacteria were significantly higher in group 2 than in groups 1 and 3 (P < 0.01), but they showed no difference between the latter two groups (P > 0.3). The protein expressions of oxidative stress (NOX-1/NOX-2/oxidized protein), apoptosis (cleaved-caspase-3/cleaved-PARP), DNA-damaged marker (γ-H2AX), fibrosis (TGF-β/Smad3) and inflammatory signaling (TLR-4/MYD88/Mal/TRAF6/p-IκBα/p-NFκB/TNF-α/MMP-9/COX-2) were significantly higher in group 2 than in group 1, and were significantly reduced in group 3 (all P < 0.001). The cellular expressions of inflammatory (CD14+/CD68+/MIF+/MMP-9), immunoreactive (CD4+/CD8+) and cytokeratin (CK17/CK18) biomarkers, and collagen-deposition/fibrotic areas as well as bladder-damaged score/disruption of the bladder mucosa displayed an identical pattern compared to that of oxidative stress among the three groups (all P < 0.0001). CONCLUSION: The long-term effect of ECSW treatment was reliable on protecting the urinary bladder from radiation-induced CC. AJTR
BACKGROUND: This study tested the long-term effect of extracorporeal shock wave (ECSW) therapy on ameliorating radiotherapy-induced chronic cystitis (CC) in rat. METHODS AND RESULTS: Adult-female SD rats (n = 24) were equally categorized into group 1 (normal control), group 2 (CC induced by radiotherapy with 450 cGy twice with a four-hour interval to the urinary bladder), group 3 [CC with ECSW treatment (0.1 mJ/mm2/120 impulses once every 3 days after radiotherapy)]. Bladder specimens were harvested by day 60 after radiotherapy. By day 60, the degree of detrusor contraction was significantly reduced in group 2 than groups 1 and 3, and significantly reduced in group 3 than in group 1 (P < 0.0001). Number of WBC, occulted blood and bacteria were significantly higher in group 2 than in groups 1 and 3 (P < 0.01), but they showed no difference between the latter two groups (P > 0.3). The protein expressions of oxidative stress (NOX-1/NOX-2/oxidized protein), apoptosis (cleaved-caspase-3/cleaved-PARP), DNA-damaged marker (γ-H2AX), fibrosis (TGF-β/Smad3) and inflammatory signaling (TLR-4/MYD88/Mal/TRAF6/p-IκBα/p-NFκB/TNF-α/MMP-9/COX-2) were significantly higher in group 2 than in group 1, and were significantly reduced in group 3 (all P < 0.001). The cellular expressions of inflammatory (CD14+/CD68+/MIF+/MMP-9), immunoreactive (CD4+/CD8+) and cytokeratin (CK17/CK18) biomarkers, and collagen-deposition/fibrotic areas as well as bladder-damaged score/disruption of the bladder mucosa displayed an identical pattern compared to that of oxidative stress among the three groups (all P < 0.0001). CONCLUSION: The long-term effect of ECSW treatment was reliable on protecting the urinary bladder from radiation-induced CC. AJTR
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