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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 reactive oxygen species (ROS)/reactive nitrogen species (RNS) and 3-nitrotyrosine (3-NT) in the urinary bladder and the antioxidant, Tempol, reduces expression. (a) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased ROS/RNS expression in urothelium and detrusor that was significantly (P ≤ 0.01) reduced with Tempol. Basal expression and CYP-induced ROS/RNS expression were significantly (P ≤ 0.01) greater in detrusor compared to urothelium. Tempol was without effect on ROS/RNS expression in urothelium and detrusor from control (no CYP) rats. (b) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased ROS/RNS expression in urinary bladder that was significantly (P ≤ 0.01) reduced with Tempol. Tempol was without effect on 3-NT expression in urinary bladder from control (no CYP) rats. *P ≤ 0.01. n = 6 for control and treatment groups.
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fig1: Cyclophosphamide- (CYP-) induced cystitis increases reactive oxygen species (ROS)/reactive nitrogen species (RNS) and 3-nitrotyrosine (3-NT) in the urinary bladder and the antioxidant, Tempol, reduces expression. (a) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased ROS/RNS expression in urothelium and detrusor that was significantly (P ≤ 0.01) reduced with Tempol. Basal expression and CYP-induced ROS/RNS expression were significantly (P ≤ 0.01) greater in detrusor compared to urothelium. Tempol was without effect on ROS/RNS expression in urothelium and detrusor from control (no CYP) rats. (b) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased ROS/RNS expression in urinary bladder that was significantly (P ≤ 0.01) reduced with Tempol. Tempol was without effect on 3-NT expression in urinary bladder from control (no CYP) rats. *P ≤ 0.01. n = 6 for control and treatment groups.

Mentions: We determined the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the urinary bladder following CYP treatment (4 hr, 48 hr) and in the presence of the antioxidant, Tempol. 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased the total free radical presence in the detrusor and urothelium that was significantly reduced (P ≤ 0.01) by Tempol (1 mM) delivered in the drinking water (Figure 1(a)). With both 4 hr and 48 hr CYP-induced cystitis, the increase in total free radical presence was significantly (P ≤ 0.01) greater in the detrusor compared to the urothelium (Figure 1(a)). Basal expression of total free radical presence in the detrusor was significantly (P ≤ 0.01) greater in the detrusor compared to the urothelium (Figure 1(a)).


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 reactive oxygen species (ROS)/reactive nitrogen species (RNS) and 3-nitrotyrosine (3-NT) in the urinary bladder and the antioxidant, Tempol, reduces expression. (a) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased ROS/RNS expression in urothelium and detrusor that was significantly (P ≤ 0.01) reduced with Tempol. Basal expression and CYP-induced ROS/RNS expression were significantly (P ≤ 0.01) greater in detrusor compared to urothelium. Tempol was without effect on ROS/RNS expression in urothelium and detrusor from control (no CYP) rats. (b) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased ROS/RNS expression in urinary bladder that was significantly (P ≤ 0.01) reduced with Tempol. Tempol was without effect on 3-NT expression in urinary bladder from control (no CYP) rats. *P ≤ 0.01. n = 6 for control and treatment groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Cyclophosphamide- (CYP-) induced cystitis increases reactive oxygen species (ROS)/reactive nitrogen species (RNS) and 3-nitrotyrosine (3-NT) in the urinary bladder and the antioxidant, Tempol, reduces expression. (a) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased ROS/RNS expression in urothelium and detrusor that was significantly (P ≤ 0.01) reduced with Tempol. Basal expression and CYP-induced ROS/RNS expression were significantly (P ≤ 0.01) greater in detrusor compared to urothelium. Tempol was without effect on ROS/RNS expression in urothelium and detrusor from control (no CYP) rats. (b) 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased ROS/RNS expression in urinary bladder that was significantly (P ≤ 0.01) reduced with Tempol. Tempol was without effect on 3-NT expression in urinary bladder from control (no CYP) rats. *P ≤ 0.01. n = 6 for control and treatment groups.
Mentions: We determined the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the urinary bladder following CYP treatment (4 hr, 48 hr) and in the presence of the antioxidant, Tempol. 4 hr and 48 hr CYP-induced cystitis significantly (P ≤ 0.01) increased the total free radical presence in the detrusor and urothelium that was significantly reduced (P ≤ 0.01) by Tempol (1 mM) delivered in the drinking water (Figure 1(a)). With both 4 hr and 48 hr CYP-induced cystitis, the increase in total free radical presence was significantly (P ≤ 0.01) greater in the detrusor compared to the urothelium (Figure 1(a)). Basal expression of total free radical presence in the detrusor was significantly (P ≤ 0.01) greater in the detrusor compared to the urothelium (Figure 1(a)).

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