title: Involvement of nitric oxide and hyperbaric oxygen in the pathogenesis of cyclophosphamide induced hemorrhagic cystitis in rats.
abstract: OBJECTIVE
  We evaluated the relationship between nitric oxide and hyperbaric oxygenation in the pathogenesis and treatment of cyclophosphamide induced hemorrhagic cystitis in rats.
  
  
  METHODS
  Cyclophosphamide (100 mg/kg) was injected in male Sprague-Dawley rats for cystitis induction. Animals were treated before and the day after cyclophosphamide injection with 100 mg/kg of the nitric oxide substrate L-arginine, 20 mg/kg of the nonselective nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester and 20 mg/kg of the selective inducible nitric oxide synthase inhibitor S-methylisothiourea. Animals were exposed to hyperbaric oxygen (2.8 atmospheres absolute for 90 minutes twice daily) with or without the administration of L-arginine and nitric oxide synthase inhibitors.
  
  
  RESULTS
  Cyclophosphamide injection resulted in severe cystitis. S-methylisothiourea produced marked inhibition of cyclophosphamide induced bladder tissue damage. L-arginine and L-NG-nitroarginine methyl ester failed to a show meaningful protective effect. Hyperbaric oxygen protected the bladder only against ulceration. Moreover, hyperbaric oxygen did not contribute to the protective effects of L-arginine, L-NG-nitroarginine methyl ester or S-methylisothiourea.
  
  
  CONCLUSIONS
  Nitric oxide produced by inducible nitric oxide synthase is an important mediator in the pathogenesis of cyclophosphamide induced cystitis. Hyperbaric oxygen has a beneficial effect on repairing bladder damage rather than on bladder protection.
authors.affiliation: Department of Physiology, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Korkmaz
authors.forename: Sukru
authors.initials: S
authors.lastname: Oter
authors.forename: Salih
authors.initials: S
authors.lastname: Deveci
authors.forename: Taner
authors.initials: T
authors.lastname: Ozgurtas
authors.forename: Turgut
authors.initials: T
authors.lastname: Topal
authors.forename: Serdar
authors.initials: S
authors.lastname: Sadir
authors.forename: Hayati
authors.initials: H
authors.lastname: Bilgic
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D001120:Arginine / Q000494:pharmacology; D003520:Cyclophosphamide / Q000633:toxicity*; D003556:Cystitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006470:Hemorrhage; D006931:Hyperbaric Oxygenation; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007550:Isothiuronium; D009569:Nitric Oxide; D003520:Cyclophosphamide; D001120:Arginine; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium; D019331:NG-Nitroarginine Methyl Ester