The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes

We hypothesized that cyclophosphamide- (CYP-) induced cystitis results in oxidative stress and contributes to urinary bladder dysfunction. We determined (1) the expression of oxidative stress markers 3-nitrotyrosine (3-NT), reactive oxygen species (ROS)/reactive nitrogen species (RNS), inflammatory...

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Main Authors: Eric J. Gonzalez, Abbey Peterson, Susan Malley, Mitchel Daniel, Daniel Lambert, Michael Kosofsky, Margaret A. Vizzard
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1155/2015/545048
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author Eric J. Gonzalez
Abbey Peterson
Susan Malley
Mitchel Daniel
Daniel Lambert
Michael Kosofsky
Margaret A. Vizzard
author_facet Eric J. Gonzalez
Abbey Peterson
Susan Malley
Mitchel Daniel
Daniel Lambert
Michael Kosofsky
Margaret A. Vizzard
author_sort Eric J. Gonzalez
collection DOAJ
description We hypothesized that cyclophosphamide- (CYP-) induced cystitis results in oxidative stress and contributes to urinary bladder dysfunction. We determined (1) the expression of oxidative stress markers 3-nitrotyrosine (3-NT), reactive oxygen species (ROS)/reactive nitrogen species (RNS), inflammatory modulators, neuropeptides calcitonin gene-related peptide (CGRP), substance P (Sub P), and adenosine triphosphate (ATP) that contribute to the inflammatory process in the urinary tract and (2) the functional role of oxidative stress in urinary bladder dysfunction with an antioxidant, Tempol, (1 mM in drinking water) combined with conscious cystometry. In CYP-treated (4 hr or 48 hr; 150 mg/kg, i.p.) rats, ROS/RNS and 3-NT significantly (P≤0.01) increased in urinary bladder. CYP treatment increased ATP, Sub P, and CGRP expression in the urinary bladder and cystometric fluid. In CYP-treated rats, Tempol significantly (P≤0.01) increased bladder capacity and reduced voiding frequency compared to CYP-treated rats without Tempol. Tempol significantly (P≤0.01) reduced ATP expression, 3-NT, and ROS/RNS expression in the urinary tract of CYP-treated rats. These studies demonstrate that reducing oxidative stress in CYP-induced cystitis improves urinary bladder function and reduces markers of oxidative stress and inflammation.
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spelling doaj-art-ac6a9382fa884d608a2b81fb0ad3bc272025-08-20T02:20:22ZengWileyThe Scientific World Journal2356-61401537-744X2015-01-01201510.1155/2015/545048545048The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition ReflexesEric J. Gonzalez0Abbey Peterson1Susan Malley2Mitchel Daniel3Daniel Lambert4Michael Kosofsky5Margaret A. Vizzard6Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USADepartment of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USADepartment of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USADepartment of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USADepartment of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USADepartment of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USADepartment of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USAWe hypothesized that cyclophosphamide- (CYP-) induced cystitis results in oxidative stress and contributes to urinary bladder dysfunction. We determined (1) the expression of oxidative stress markers 3-nitrotyrosine (3-NT), reactive oxygen species (ROS)/reactive nitrogen species (RNS), inflammatory modulators, neuropeptides calcitonin gene-related peptide (CGRP), substance P (Sub P), and adenosine triphosphate (ATP) that contribute to the inflammatory process in the urinary tract and (2) the functional role of oxidative stress in urinary bladder dysfunction with an antioxidant, Tempol, (1 mM in drinking water) combined with conscious cystometry. In CYP-treated (4 hr or 48 hr; 150 mg/kg, i.p.) rats, ROS/RNS and 3-NT significantly (P≤0.01) increased in urinary bladder. CYP treatment increased ATP, Sub P, and CGRP expression in the urinary bladder and cystometric fluid. In CYP-treated rats, Tempol significantly (P≤0.01) increased bladder capacity and reduced voiding frequency compared to CYP-treated rats without Tempol. Tempol significantly (P≤0.01) reduced ATP expression, 3-NT, and ROS/RNS expression in the urinary tract of CYP-treated rats. These studies demonstrate that reducing oxidative stress in CYP-induced cystitis improves urinary bladder function and reduces markers of oxidative stress and inflammation.http://dx.doi.org/10.1155/2015/545048
spellingShingle Eric J. Gonzalez
Abbey Peterson
Susan Malley
Mitchel Daniel
Daniel Lambert
Michael Kosofsky
Margaret A. Vizzard
The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes
The Scientific World Journal
title The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes
title_full The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes
title_fullStr The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes
title_full_unstemmed The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes
title_short The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes
title_sort effects of tempol on cyclophosphamide induced oxidative stress in rat micturition reflexes
url http://dx.doi.org/10.1155/2015/545048
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