122 THERAPEUTIC EFFECT OF TAC-302, A NOVEL NEURITE OUTGROWTH ENHANCER, ON VOIDING DYSFUNCTION IN RATS WITH STZ-INDUCED DIABETES

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research (II)1 Apr 2013122 THERAPEUTIC EFFECT OF TAC-302, A NOVEL NEURITE OUTGROWTH ENHANCER, ON VOIDING DYSFUNCTION IN RATS WITH STZ-INDUCED DIABETES Takahisa Noma, Shohei Yoshida, Atsushi Hakozaki, Naoki Orimoto, Eiji Sasaki, and Yukio Hayashi Takahisa NomaTakahisa Noma Tsukuba-shi, Ibaraki, Japan More articles by this author , Shohei YoshidaShohei Yoshida Tsukuba-shi, Ibaraki, Japan More articles by this author , Atsushi HakozakiAtsushi Hakozaki Tsukuba-shi, Ibaraki, Japan More articles by this author , Naoki OrimotoNaoki Orimoto Tsukuba-shi, Ibaraki, Japan More articles by this author , Eiji SasakiEiji Sasaki Tsukuba-shi, Ibaraki, Japan More articles by this author , and Yukio HayashiYukio Hayashi Tsukuba-shi, Ibaraki, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1501AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It has been reported that decreased bladder sensation, contractility and compliance of detrusor occurred in approximately 40-85% of patients with diabetic cystopathy. These voiding dysfunctions are known to be induced primarily by diabetic neuropathy. TAC-302, cyclohexenoic-long fatty alcohol derivative, is a novel neurite outgrowth enhancer which has a beneficial effect on peripheral neuropathy and improved nerve conductance velocity in rats with diabetes mellitus (DM) induced by streptozotocin (STZ). Therefore, we investigated the effect of oral treatment with TAC-302 on voiding functions in STZ-induced diabetic rats. METHODS STZ-induced DM rats were orally treated with vehicle, TAC-302 (2-60 mg/kg, b.i.d.), distigmine (acetylcholine esterase inhibitor: 0.6 mg/kg, b.i.d.), or bethanechol (muscarinic receptor agonist: 60 mg/kg, b.i.d.). The treatments were started from 4 weeks after the induction of DM and continued for 4 weeks. Eight weeks after the induction of DM, voiding functions were evaluated by single cystometry. RESULTS Significant increase of micturition volume, residual urine volume and bladder capacity, and significant decrease of micturition efficiency were observed in DM rats compared with sham-operated rats. This indicates that STZ-induced diabetic rats show the feature of diabetic cystopathy. TAC-302 dose-dependently reduced the residual urine volume and increased the micturition efficiency compared with DM vehicle group. By contrast, these parameters were not improved by chronic treatments with distigmine and bethanechol. CONCLUSIONS These results indicate that TAC-302 therapeutically recover voiding dysfunctions in STZ-induced diabetic rats. Furthermore, it is found that the effect of TAC-302 is pharmacologically different from those of acetylcholine esterase inhibitor and muscarinic receptor agonist. Therefore, TAC-302 could be therapeutic medicine to treat voiding dysfunctions such as diabetic cystopathy. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e49 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takahisa Noma Tsukuba-shi, Ibaraki, Japan More articles by this author Shohei Yoshida Tsukuba-shi, Ibaraki, Japan More articles by this author Atsushi Hakozaki Tsukuba-shi, Ibaraki, Japan More articles by this author Naoki Orimoto Tsukuba-shi, Ibaraki, Japan More articles by this author Eiji Sasaki Tsukuba-shi, Ibaraki, Japan More articles by this author Yukio Hayashi Tsukuba-shi, Ibaraki, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...