107 THERAPEUTIC EFFECTS OF THE CYCLOHEXENONE DERIVATIVE TAC-302 ON THE BLADDER DYSFUNCTION IN STREPTOZOTOCIN (STZ)-INDUCED DIABETIC RATS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research II1 Apr 2012107 THERAPEUTIC EFFECTS OF THE CYCLOHEXENONE DERIVATIVE TAC-302 ON THE BLADDER DYSFUNCTION IN STREPTOZOTOCIN (STZ)-INDUCED DIABETIC RATS Tsuyoshi Yoshizawa, Yukio Hayashi, Akira Yoshida, Yoshihiko Ito, Shizuo Yamada, and Satoru Takahashi Tsuyoshi YoshizawaTsuyoshi Yoshizawa Tokyo, Japan More articles by this author , Yukio HayashiYukio Hayashi Tsukuba, Japan More articles by this author , Akira YoshidaAkira Yoshida Shizuoka, Japan More articles by this author , Yoshihiko ItoYoshihiko Ito Shizuoka, Japan More articles by this author , Shizuo YamadaShizuo Yamada Shizuoka, Japan More articles by this author , and Satoru TakahashiSatoru Takahashi Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.155AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent studies have shown that there are significant serial changes in lower urinary tract dysfunction in diabetic patients. Briefly, overactive bladder (OAB) symptoms such as urgency and pollakisuria are often observed in the early phase of the disease. Furthermore, also in the early phase, most patients complain of severe nocturia due to diabetes-related polydipsia and polyuria. TAC-302 is a cyclohexenone derivative that induces neuronal growth and reportedly improves voiding dysfunction of rat models. We therefore evaluated the effects of TAC-302 on diabetic bladder dysfunction, using streptozotocin (STZ)-induced diabetic rats. METHODS Seven-week-old female Wistar rats were divided into sham and DM (STZ 50 mg/kg, i.p.) groups. At weeks 1, 4, 8, and 12, we recorded a 24-hour frequency volume chart, cystometry, muscle strip contractions induced by electrical field stimulation (EFS), carbachol, and α,β-methylene ATP (α,β-mATP). Muscarinic and P2X receptor levels of the bladder were also measured by radioreceptor assay with [3H]NMS and [3H]α,β-mATP as labeling ligands, respectively. Thereafter, we administered TAC-302 (8mg/kg, i.p., daily for 4 weeks) and performed similar experiments in three groups (sham, DM+vehicle, DM+TAC-302) at week 4. RESULTS In STZ-induced diabetic rats, we observed polydipsic and polyuric pollakisuria in 24-hour frequency volume chart and increased residual urine in cystometry at all weeks. Muscle strip studies showed increased detrusor contractile responses in STZ rats, which were associated with the increased number of bladder muscarinic and P2X receptors in the radioreceptor assay. In TAC-302 experiments, we identified significantly increased tidal voided volume and reduced residual urine in the DM+TAC-302 group compared to the DM+vehicle group. Significant inhibition of detrusor contraction responses were also observed in the DM+TAC-302 group compared to the DM+Vehicle group, in association with the decreased number of bladder muscarinic and P2X receptors. CONCLUSIONS These results indicate that TAC-302 can suppress bladder overactivity and normalize voiding dysfunction in diabetic rats. Thus, TAC-302 is a promising agent that could improve diabetes-induced lower urinary tract symptoms, in which voiding and storage symptoms coexist. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e43 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tsuyoshi Yoshizawa Tokyo, Japan More articles by this author Yukio Hayashi Tsukuba, Japan More articles by this author Akira Yoshida Shizuoka, Japan More articles by this author Yoshihiko Ito Shizuoka, Japan More articles by this author Shizuo Yamada Shizuoka, Japan More articles by this author Satoru Takahashi Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...