OBJECTIVE: To examine the effects of suplatast tosilate (IPD-1151T), a Th2 cytokine inhibitor recently recognized to improve the symptoms in patients with interstitial cystitis (IC), in a rat model of HCl-induced chronic cystitis, to elucidate the possible mechanisms by which the drug improves the symptoms of IC. MATERIALS AND METHODS: Chronic cystitis was induced by intravesical instillation of 0.2 mL of 0.4 m HCl in female adult rats. After a once-daily oral administration of IPD-1151T (0.1-100 mg/kg) or prednisolone (5 mg/kg) for 7 days, cystometry was performed under urethane anaesthesia. The bladder from HCl-induced cystitis rats was also assessed histopathologically. RESULTS: On cystometrography there was frequent voiding in cystitis rats. Administration of IPD-1151T for 7 days after intravesical HCl instillation dose-dependently increased the micturition volume and intercontraction intervals. Treatment with prednisolone had similar therapeutic effects. Histological analyses in the bladder from cystitis rats revealed oedema and infiltration of inflammatory cells such as mast cells and eosinophils in the lamina propria and the transitional epithelial thickening. These histological changes and the number of mast cells and eosinophils were reduced by administration of IPD-1151T or prednisolone. CONCLUSION: The present results indicate that IPD-1151T improves bladder function and pathological changes in HCl-induced cystitis rats, as previously observed in patients with IC. The rat cystitis model induced by HCl could provide useful information for studying proposed therapies for IC which might involve T cell-dependent inflammatory responses as one of its potential pathophysiologies.
OBJECTIVE: To examine the effects of suplatast tosilate (IPD-1151T), a Th2 cytokine inhibitor recently recognized to improve the symptoms in patients with interstitial cystitis (IC), in a rat model of HCl-induced chronic cystitis, to elucidate the possible mechanisms by which the drug improves the symptoms of IC. MATERIALS AND METHODS:Chronic cystitis was induced by intravesical instillation of 0.2 mL of 0.4 m HCl in female adult rats. After a once-daily oral administration of IPD-1151T (0.1-100 mg/kg) or prednisolone (5 mg/kg) for 7 days, cystometry was performed under urethane anaesthesia. The bladder from HCl-induced cystitisrats was also assessed histopathologically. RESULTS: On cystometrography there was frequent voiding in cystitisrats. Administration of IPD-1151T for 7 days after intravesical HCl instillation dose-dependently increased the micturition volume and intercontraction intervals. Treatment with prednisolone had similar therapeutic effects. Histological analyses in the bladder from cystitisrats revealed oedema and infiltration of inflammatory cells such as mast cells and eosinophils in the lamina propria and the transitional epithelial thickening. These histological changes and the number of mast cells and eosinophils were reduced by administration of IPD-1151T or prednisolone. CONCLUSION: The present results indicate that IPD-1151T improves bladder function and pathological changes in HCl-induced cystitisrats, as previously observed in patients with IC. The ratcystitis model induced by HCl could provide useful information for studying proposed therapies for IC which might involve T cell-dependent inflammatory responses as one of its potential pathophysiologies.
Authors: Yukio Hayashi; Koichi Takimoto; Michael B Chancellor; Kristin A Erickson; Vickie L Erickson; Tsukasa Kirimoto; Koushi Nakano; William C de Groat; Naoki Yoshimura Journal: Am J Physiol Regul Integr Comp Physiol Date: 2009-03-11 Impact factor: 3.619
Authors: Susan Keay; Samantha Leitzell; Ashley Ochrzcin; George Clements; Min Zhan; David Johnson Journal: BMC Urol Date: 2012-06-08 Impact factor: 2.264