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The effects of tempol on cyclophosphamide-induced oxidative stress in rat micturition reflexes.

Gonzalez EJ, Peterson A, Malley S, Daniel M, Lambert D, Kosofsky M, Vizzard MA - ScientificWorldJournal (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Cyclophosphamide- (CYP-) induced cystitis increases calcitonin gene-related peptide (CGRP) in the urinary bladder and cystometric fluid and the antioxidant, Tempol, reduces expression. (a) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased CGRP expression in urinary bladder that was significantly (P ≤ 0.01) reduced with Tempol. Tempol was without effect on CGRP expression in urinary bladder from control (no CYP) rats. (b) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased CGRP expression in cystometric fluid that was significantly (P ≤ 0.01) reduced with Tempol. *P ≤ 0.01. n = 6 for control and treatment groups.
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fig3: Cyclophosphamide- (CYP-) induced cystitis increases calcitonin gene-related peptide (CGRP) in the urinary bladder and cystometric fluid and the antioxidant, Tempol, reduces expression. (a) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased CGRP expression in urinary bladder that was significantly (P ≤ 0.01) reduced with Tempol. Tempol was without effect on CGRP expression in urinary bladder from control (no CYP) rats. (b) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased CGRP expression in cystometric fluid that was significantly (P ≤ 0.01) reduced with Tempol. *P ≤ 0.01. n = 6 for control and treatment groups.

Mentions: The neuropeptides, Sub P and CGRP, are known modulators of inflammation and may contribute to the pathogenesis of many diseases including migraine, asthma, and urinary bladder inflammation [4, 20, 39, 40]. 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased Sub P and CGRP expression in the urinary bladder (Figures 2(a) and 3(a)) and cystometric fluid (Figures 2(b) and 3(b)) that was significantly reduced (P ≤ 0.01) by Tempol (1 mM) delivered in the drinking water (Figures 2(a), 2(b), 3(a) and 3(b)). Sub P expression in the urinary bladder was similar following 4 hr and 48 hr CYP-induced cystitis in the urinary bladder and cystometric fluid (Figures 2(a) and 2(b)). In contrast, 48 hr CYP-induced cystitis resulted in significantly (P ≤ 0.01) greater CGRP expression in the urinary bladder and cystometric fluid compared to the 4 hr time point (Figures 3(a) and 3(b)).


The effects of tempol on cyclophosphamide-induced oxidative stress in rat micturition reflexes.

Gonzalez EJ, Peterson A, Malley S, Daniel M, Lambert D, Kosofsky M, Vizzard MA - ScientificWorldJournal (2015)

Cyclophosphamide- (CYP-) induced cystitis increases calcitonin gene-related peptide (CGRP) in the urinary bladder and cystometric fluid and the antioxidant, Tempol, reduces expression. (a) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased CGRP expression in urinary bladder that was significantly (P ≤ 0.01) reduced with Tempol. Tempol was without effect on CGRP expression in urinary bladder from control (no CYP) rats. (b) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased CGRP expression in cystometric fluid that was significantly (P ≤ 0.01) reduced with Tempol. *P ≤ 0.01. n = 6 for control and treatment groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4417973&req=5

fig3: Cyclophosphamide- (CYP-) induced cystitis increases calcitonin gene-related peptide (CGRP) in the urinary bladder and cystometric fluid and the antioxidant, Tempol, reduces expression. (a) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased CGRP expression in urinary bladder that was significantly (P ≤ 0.01) reduced with Tempol. Tempol was without effect on CGRP expression in urinary bladder from control (no CYP) rats. (b) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased CGRP expression in cystometric fluid that was significantly (P ≤ 0.01) reduced with Tempol. *P ≤ 0.01. n = 6 for control and treatment groups.
Mentions: The neuropeptides, Sub P and CGRP, are known modulators of inflammation and may contribute to the pathogenesis of many diseases including migraine, asthma, and urinary bladder inflammation [4, 20, 39, 40]. 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased Sub P and CGRP expression in the urinary bladder (Figures 2(a) and 3(a)) and cystometric fluid (Figures 2(b) and 3(b)) that was significantly reduced (P ≤ 0.01) by Tempol (1 mM) delivered in the drinking water (Figures 2(a), 2(b), 3(a) and 3(b)). Sub P expression in the urinary bladder was similar following 4 hr and 48 hr CYP-induced cystitis in the urinary bladder and cystometric fluid (Figures 2(a) and 2(b)). In contrast, 48 hr CYP-induced cystitis resulted in significantly (P ≤ 0.01) greater CGRP expression in the urinary bladder and cystometric fluid compared to the 4 hr time point (Figures 3(a) and 3(b)).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus