Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models

Objectives. It is still not clear how the intravesical instillation of drugs affects rat urinary frequency. This study aimed to examine the dynamics of intravesical treatments’ treatment effect on rat urinary frequency models by real-time and extended monitoring using a novel continuous urination mo...

Full description

Saved in:
Bibliographic Details
Main Authors: Tomofumi Watanabe, Takuya Sadahira, Yusuke Tominaga, Yuki Maruyama, Naoya Nagasaki, Takanori Sekito, Kohei Edamura, Toyohiko Watanabe, Motoo Araki, Masami Watanabe
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Veterinary Medicine International
Online Access:http://dx.doi.org/10.1155/2024/6505595
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832546215620771840
author Tomofumi Watanabe
Takuya Sadahira
Yusuke Tominaga
Yuki Maruyama
Naoya Nagasaki
Takanori Sekito
Kohei Edamura
Toyohiko Watanabe
Motoo Araki
Masami Watanabe
author_facet Tomofumi Watanabe
Takuya Sadahira
Yusuke Tominaga
Yuki Maruyama
Naoya Nagasaki
Takanori Sekito
Kohei Edamura
Toyohiko Watanabe
Motoo Araki
Masami Watanabe
author_sort Tomofumi Watanabe
collection DOAJ
description Objectives. It is still not clear how the intravesical instillation of drugs affects rat urinary frequency. This study aimed to examine the dynamics of intravesical treatments’ treatment effect on rat urinary frequency models by real-time and extended monitoring using a novel continuous urination monitoring system. Methods. Nine eleven-week-old female Wistar rats were divided into three groups to receive intravesical instillation of 0.1% acetic acid (AA), 1.0% AA, or phosphate-buffered saline (PBS). Thirty minutes later, these drugs were voided, and rats were moved to a continuous urination monitoring system, UM-100. UM-100 monitored rat urination quantitatively and continuously for 24 hours. Rats were then euthanized, and histopathologic examinations using a damage score validated the severity of bladder inflammation. We used nine additional rats to determine the treatment effect of various drugs against the urinary frequency. These rats were also treated with 1.0% AA in the same way and divided into three groups (n = 3 each) to receive intravesical instillation of lidocaine, silver nitrate (AgNO3), or dimethyl sulfoxide (DMSO), respectively. Thirty minutes later, rats were catheterized again and moved to the UM-100, and their voiding was monitored for 24 hours. Results. Intravesical instillation of AA increased the urinary frequency and decreased the mean voided volume (VV) in a concentration-dependent manner, with statistical significance at a concentration of 1.0% (urinary frequency; p=0.0007, mean VV; p=0.0032, respectively) compared with PBS. Histopathological analysis of these models demonstrated a significantly higher damage score of bladder mucosa in both 0.1% AA and 1.0% AA compared with PBS, with the severity in concordance with the clinical severity of urinary frequency (0.1% AA: p<0.0001, 1.0% AA: p<0.0001). Moreover, intravesical instillation of lidocaine, AgNO3, and DMSO decreased the urinary frequency. Continuous monitoring with UM-100 also demonstrated that the treatment effect of these intravesically instilled drugs occurred only at night. Conclusions. The extended monitoring of rat urination by UM-100 revealed a significant fluctuation in the treatment effect of intravesically instilled drugs between day and night. These findings may help establish novel therapies for urinary frequency.
format Article
id doaj-art-b2f5361da2064d329a976b787dc02337
institution Kabale University
issn 2042-0048
language English
publishDate 2024-01-01
publisher Wiley
record_format Article
series Veterinary Medicine International
spelling doaj-art-b2f5361da2064d329a976b787dc023372025-02-03T07:23:37ZengWileyVeterinary Medicine International2042-00482024-01-01202410.1155/2024/6505595Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency ModelsTomofumi Watanabe0Takuya Sadahira1Yusuke Tominaga2Yuki Maruyama3Naoya Nagasaki4Takanori Sekito5Kohei Edamura6Toyohiko Watanabe7Motoo Araki8Masami Watanabe9Department of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyObjectives. It is still not clear how the intravesical instillation of drugs affects rat urinary frequency. This study aimed to examine the dynamics of intravesical treatments’ treatment effect on rat urinary frequency models by real-time and extended monitoring using a novel continuous urination monitoring system. Methods. Nine eleven-week-old female Wistar rats were divided into three groups to receive intravesical instillation of 0.1% acetic acid (AA), 1.0% AA, or phosphate-buffered saline (PBS). Thirty minutes later, these drugs were voided, and rats were moved to a continuous urination monitoring system, UM-100. UM-100 monitored rat urination quantitatively and continuously for 24 hours. Rats were then euthanized, and histopathologic examinations using a damage score validated the severity of bladder inflammation. We used nine additional rats to determine the treatment effect of various drugs against the urinary frequency. These rats were also treated with 1.0% AA in the same way and divided into three groups (n = 3 each) to receive intravesical instillation of lidocaine, silver nitrate (AgNO3), or dimethyl sulfoxide (DMSO), respectively. Thirty minutes later, rats were catheterized again and moved to the UM-100, and their voiding was monitored for 24 hours. Results. Intravesical instillation of AA increased the urinary frequency and decreased the mean voided volume (VV) in a concentration-dependent manner, with statistical significance at a concentration of 1.0% (urinary frequency; p=0.0007, mean VV; p=0.0032, respectively) compared with PBS. Histopathological analysis of these models demonstrated a significantly higher damage score of bladder mucosa in both 0.1% AA and 1.0% AA compared with PBS, with the severity in concordance with the clinical severity of urinary frequency (0.1% AA: p<0.0001, 1.0% AA: p<0.0001). Moreover, intravesical instillation of lidocaine, AgNO3, and DMSO decreased the urinary frequency. Continuous monitoring with UM-100 also demonstrated that the treatment effect of these intravesically instilled drugs occurred only at night. Conclusions. The extended monitoring of rat urination by UM-100 revealed a significant fluctuation in the treatment effect of intravesically instilled drugs between day and night. These findings may help establish novel therapies for urinary frequency.http://dx.doi.org/10.1155/2024/6505595
spellingShingle Tomofumi Watanabe
Takuya Sadahira
Yusuke Tominaga
Yuki Maruyama
Naoya Nagasaki
Takanori Sekito
Kohei Edamura
Toyohiko Watanabe
Motoo Araki
Masami Watanabe
Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models
Veterinary Medicine International
title Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models
title_full Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models
title_fullStr Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models
title_full_unstemmed Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models
title_short Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models
title_sort circadian rhythms fluctuate the treatment effects of intravesical treatments on rat urinary frequency models
url http://dx.doi.org/10.1155/2024/6505595
work_keys_str_mv AT tomofumiwatanabe circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels
AT takuyasadahira circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels
AT yusuketominaga circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels
AT yukimaruyama circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels
AT naoyanagasaki circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels
AT takanorisekito circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels
AT koheiedamura circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels
AT toyohikowatanabe circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels
AT motooaraki circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels
AT masamiwatanabe circadianrhythmsfluctuatethetreatmenteffectsofintravesicaltreatmentsonraturinaryfrequencymodels