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: Sukru Oter, Ahmet Korkmaz, Emin Oztas, Ibrahim Yildirim, Turgut Topal, Hayati Bilgic
• Journal: Urological research (Urol Res) Vol. 32 Issue 3 Pg. 185-9 (Jun 2004) ISSN: 0300-5623 [Print] Germany
• PMID: 15205850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Enzyme Inhibitors
• Isothiuronium
• Cyclophosphamide
• Arginine
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• S-methylisothiopseudouronium

Topics

• Animals
• Antineoplastic Agents, Alkylating
• Arginine (pharmacology)
• Cyclophosphamide
• Cystitis (chemically induced, drug therapy, pathology)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Female
• Hemorrhage (chemically induced, drug therapy, pathology)
• Isothiuronium (analogs & derivatives, pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitric Oxide Synthase Type II
• Rats
• Rats, Sprague-Dawley