Yasuhito Funahashi1, Masaki Yoshida2, Tokunori Yamamoto2, Tsuyoshi Majima2, Shun Takai2, Momokazu Gotoh2. 1. Department of Urology, Nagoya University Graduate School of Medicine, Nagoya and National Center for Geriatrics and Gerontology (MY), Ohbu, Japan. Electronic address: yfunahashi@med.nagoya-u.ac.jp. 2. Department of Urology, Nagoya University Graduate School of Medicine, Nagoya and National Center for Geriatrics and Gerontology (MY), Ohbu, Japan.
Abstract
PURPOSE: We examined the effects of intravesical application of rebamipide (Otsuka Pharmaceutical, Tokyo, Japan) on bladder inflammation and overactivity in a chemically induced cystitis model. MATERIALS AND METHODS: Female Sprague Dawley® rats under isoflurane anesthesia were injected with 150 mg/kg cyclophosphamide in the peritoneum, and 1 mM or 10 mM rebamipide or vehicle was administered in the bladder and remained for 1 hour. Control rats were injected with saline in the peritoneum and vehicle was administered in the bladder. The bladder was harvested at 48 hours. Hematoxylin and eosin staining was performed and the inflammation grade was assessed. The amount of myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proinflammatory cytokines were quantified using reverse transcriptase-polymerase chain reaction. Cystometrogram was done in awake rats 48 hours after cyclophosphamide treatment to measure voiding reflex parameters. RESULTS: Histological evaluation revealed that bladder inflammation in cyclophosphamide treated rats was suppressed by rebamipide in a dose dependent manner. Up-regulated myeloperoxidase, IL-1β, IL-6 and TNF-α expression in cyclophosphamide treated rats was also suppressed in rebamipide treated rats. Cystometrogram demonstrated that the intercontraction interval decreased in cyclophosphamide treated rats but was prolonged by rebamipide. CONCLUSIONS: Intravesical application of rebamipide suppressed bladder inflammation and overactivity in a dose dependent manner. This may provide a new treatment strategy for chemotherapy associated cystitis.
PURPOSE: We examined the effects of intravesical application of rebamipide (Otsuka Pharmaceutical, Tokyo, Japan) on bladder inflammation and overactivity in a chemically induced cystitis model. MATERIALS AND METHODS: Female Sprague Dawley® rats under isoflurane anesthesia were injected with 150 mg/kg cyclophosphamide in the peritoneum, and 1 mM or 10 mM rebamipide or vehicle was administered in the bladder and remained for 1 hour. Control rats were injected with saline in the peritoneum and vehicle was administered in the bladder. The bladder was harvested at 48 hours. Hematoxylin and eosin staining was performed and the inflammation grade was assessed. The amount of myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proinflammatory cytokines were quantified using reverse transcriptase-polymerase chain reaction. Cystometrogram was done in awake rats 48 hours after cyclophosphamide treatment to measure voiding reflex parameters. RESULTS: Histological evaluation revealed that bladder inflammation in cyclophosphamide treated rats was suppressed by rebamipide in a dose dependent manner. Up-regulated myeloperoxidase, IL-1β, IL-6 and TNF-α expression in cyclophosphamide treated rats was also suppressed in rebamipide treated rats. Cystometrogram demonstrated that the intercontraction interval decreased in cyclophosphamide treated rats but was prolonged by rebamipide. CONCLUSIONS: Intravesical application of rebamipide suppressed bladder inflammation and overactivity in a dose dependent manner. This may provide a new treatment strategy for chemotherapy associated cystitis.