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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

Summary histograms of the effects of Tempol (1 mM) on intercontraction interval (ICI; s), bladder capacity (BC; μL), and void volume (VV; mL) in CYP-treated (4 hr; 48 hr) rats. Tempol in the drinking water significantly (P ≤ 0.01) increased ICI (a), VV (b), and BC (c) in CYP-treated (4 hr and 48 hr) rats. Tempol was without effect in control (no CYP treatment) rats. #P ≤ 0.01 compared to control + vehicle (between-group difference); *P ≤ 0.01 compared to 4 hr or 48 hr CYP + vehicle (within-group difference). Sample sizes are n = 6 in control and treatment groups.
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fig5: Summary histograms of the effects of Tempol (1 mM) on intercontraction interval (ICI; s), bladder capacity (BC; μL), and void volume (VV; mL) in CYP-treated (4 hr; 48 hr) rats. Tempol in the drinking water significantly (P ≤ 0.01) increased ICI (a), VV (b), and BC (c) in CYP-treated (4 hr and 48 hr) rats. Tempol was without effect in control (no CYP treatment) rats. #P ≤ 0.01 compared to control + vehicle (between-group difference); *P ≤ 0.01 compared to 4 hr or 48 hr CYP + vehicle (within-group difference). Sample sizes are n = 6 in control and treatment groups.

Mentions: Conscious, open outlet cystometry with continuous intravesical infusion of saline was performed in separate groups (n = 6 each) of control and CYP-treated (48 h) rats with or without Tempol (vehicle only) in the drinking water to determine bladder function (Figures 5–8).


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)

Summary histograms of the effects of Tempol (1 mM) on intercontraction interval (ICI; s), bladder capacity (BC; μL), and void volume (VV; mL) in CYP-treated (4 hr; 48 hr) rats. Tempol in the drinking water significantly (P ≤ 0.01) increased ICI (a), VV (b), and BC (c) in CYP-treated (4 hr and 48 hr) rats. Tempol was without effect in control (no CYP treatment) rats. #P ≤ 0.01 compared to control + vehicle (between-group difference); *P ≤ 0.01 compared to 4 hr or 48 hr CYP + vehicle (within-group difference). Sample sizes are n = 6 in control and treatment groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4417973&req=5

fig5: Summary histograms of the effects of Tempol (1 mM) on intercontraction interval (ICI; s), bladder capacity (BC; μL), and void volume (VV; mL) in CYP-treated (4 hr; 48 hr) rats. Tempol in the drinking water significantly (P ≤ 0.01) increased ICI (a), VV (b), and BC (c) in CYP-treated (4 hr and 48 hr) rats. Tempol was without effect in control (no CYP treatment) rats. #P ≤ 0.01 compared to control + vehicle (between-group difference); *P ≤ 0.01 compared to 4 hr or 48 hr CYP + vehicle (within-group difference). Sample sizes are n = 6 in control and treatment groups.
Mentions: Conscious, open outlet cystometry with continuous intravesical infusion of saline was performed in separate groups (n = 6 each) of control and CYP-treated (48 h) rats with or without Tempol (vehicle only) in the drinking water to determine bladder function (Figures 5–8).

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