title: Inducible nitric oxide synthase inhibition in cyclophosphamide induced hemorrhagic cystitis in rats.
abstract: Cyclophosphamide (CP) is an antineoplastic agent used alone or in combination with other chemotherapeutic agents for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major potential toxicity and dose limiting side effect of CP. Recently, it has been shown that endogenous inflammatory mediators are involved in cystitis by increasing nitric oxide (NO) production in target tissue. The aim of this study was to evaluate the relationship between NO and CP induced hemorrhagic cystitis HC in rats. A total of 30 female Spraque-Dawley rats were divided into 4 groups. Group 1 served as control, three groups received single dose of CP (100 mg/kg) intraperitoneally (i.p.): group 2 received CP only. Group 3 received the NO precursor L-arginine (80 mg/kg/day), and group 4 received the selective inducible NO synthase (iNOS) inhibitor S-methylisothiourea (SMT; 20 mg/kg/day) before and the day after cyclophosphamide injection. CP injection resulted in severe cystitis. SMT but not L-arginine produced marked inhibition of CP induced bladder damage. We concluded that NO produced by iNOS, is an important mediator in the pathogenesis of CP induced cystitis.
authors.affiliation: Gulhane Military Medical Academy, Department of Physiology, Ankara, Turkey. oters@gata.edu.tr
authors.forename: Sukru
authors.initials: S
authors.lastname: Oter
authors.forename: Ahmet
authors.initials: A
authors.lastname: Korkmaz
authors.forename: Emin
authors.initials: E
authors.lastname: Oztas
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yildirim
authors.forename: Turgut
authors.initials: T
authors.lastname: Topal
authors.forename: Hayati
authors.initials: H
authors.lastname: Bilgic
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D001120:Arginine / Q000494:pharmacology; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004791:Enzyme Inhibitors; D007550:Isothiuronium; D003520:Cyclophosphamide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C027744:S-methylisothiopseudouronium