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Effects of poly(ADP-ribose) polymerase inhibition in bladder damage caused by cyclophosphamide in rats.
- Source :
-
Experimental biology and medicine (Maywood, N.J.) [Exp Biol Med (Maywood)] 2008 Mar; Vol. 233 (3), pp. 338-43. - Publication Year :
- 2008
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Abstract
- It was previously shown that nitric oxide produced by inducible nitric oxide synthase (iNOS) and peroxynitrite are responsible for cyclophosphamide (CP)-induced cystitis. Since endogenous production of peroxynitrite is known to lead to poly(ADP-ribose) polymerase (PARP) activation, in this study, the aim was to evaluate whether the PARP activation pathway is also included in the pathogenesis of CP-induced bladder ulceration in rats. A total of 48 male albino Wistar rats were divided into 5 groups. Group 1 served as control and was given 2 ml saline; four groups received a single dose of CP (200 mg/kg) with the same time intervals. Group 2 received CP only; Group 3, selective iNOS inhibitor 1400W (20 mg/kg); Group 4, peroxynitrite scavenger ebselen (30 mg/kg); and Group 5, PARP inhibitor 3-aminobenzamide (20 mg/kg). CP injection resulted in severe cystitis with continuous macroscopic hemorrhage, strong edema, inflammation, and ulceration. Moreover, bladder iNOS activation and urine nitrite-nitrate levels were dramatically increased. Histologically, 1400W protected bladder against CP damage and decreased urine nitrite-nitrate levels and bladder iNOS induction. Ebselen has shown similar histologic results with 1400W without changing urinary nitrite-nitrate level and iNOS activity. Furthermore in the 3-aminobenzamide group, beneficial effects had also occurred including decreased ulceration. These results suggest that PARP activation involves pathogenesis of CP-induced bladder ulceration. Furthermore, PARP is not only important for ulceration but also for bladder edema, hemorrhage, and inflammation because of broken uroepithelial cellular integrity.
- Subjects :
- Animals
Biomarkers metabolism
Body Weight drug effects
Male
Nitric Oxide Synthase Type II antagonists & inhibitors
Nitric Oxide Synthase Type II metabolism
Nitrosation
Organ Size drug effects
Poly(ADP-ribose) Polymerases metabolism
Rats
Rats, Wistar
Urinary Bladder Diseases chemically induced
Urinary Bladder Diseases pathology
Cyclophosphamide pharmacology
Enzyme Inhibitors pharmacology
Poly(ADP-ribose) Polymerase Inhibitors
Urinary Bladder Diseases enzymology
Urinary Bladder Diseases prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3702
- Volume :
- 233
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Experimental biology and medicine (Maywood, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 18296739
- Full Text :
- https://doi.org/10.3181/0706-RM-151