Peroxynitrite may be involved in bladder damage caused by cyclophosphamide in rats.
OBJECTIVE
It was previously shown that nitric oxide (NO) produced by inducible NO synthase (iNOS) is responsible for cyclophosphamide (CP) induced cystitis. In this study we evaluated whether peroxynitrite is also responsible for CP induced bladder damage in rats.


METHODS
A total of 38 male albino Wistar rats were divided into 4 groups. Group 1 served as controls and was given 2 ml saline, while 3 groups received a single dose of CP (200 mg/kg) at the same intervals. Group 2 received CP only, group 3 received the selective iNOS inhibitor aminoguanidine (AG) (100 mg/kg) and group 4 received the peroxynitrite scavenger ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) (20 mg/kg).


RESULTS
CP injection resulted in severe cystitis with continuous macroscopic hemorrhage, strong edema, inflammation and ulceration. Moreover, bladder tissue malondialdehyde levels, iNOS activation and urine nitrite-nitrate levels were dramatically increased. AG histologically protected bladder against CP damage and decreased urine nitrite-nitrate levels, bladder malondialdehyde and iNOS induction. Ebselen showed results similar to those of AG without changing the urinary nitrite-nitrate level and iNOS activity.


CONCLUSIONS
These results suggest that not only nitric oxide, but also peroxynitrite may be important in the pathogenesis of CP induced cystitis.
Korkmaz
Ahmet
A
Department of Physiology, Gulhane Military Medical Academy, Ankara, Turkey. korkmaza@gata.edu.tr
Oter
Sukru
S
Sadir
Serdar
S
Coskun
Omer
O
Topal
Turgut
T
Ozler
Mehmet
M
Bilgic
Hayati
H
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001393:Azoles / Q000008:administration & dosage / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000009:adverse effects*; D006146:Guanidines / Q000008:administration & dosage / Q000009:adverse effects*; D054833:Isoindoles; D008297:Male; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D030421:Peroxynitrous Acid / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D001393:Azoles; D016166:Free Radical Scavengers; D006146:Guanidines; D054833:Isoindoles; D016566:Organoselenium Compounds; D030421:Peroxynitrous Acid; C042986:ebselen; D003520:Cyclophosphamide; C004479:pimagedine