[abstract] Involvement Of Nitric Oxide And Hyperbaric Oxygen In The Pathogenesis Of Cyclophosphamide Induced Hemorrhagic Cystitis In Rats

Abstract

Purpose: The aim of this study was to evaluate the relationship between nitric oxide and hyperbaric oxygenation in the pathogenesis and treatment of cyclophosphamide-induced hemorrhagic cystitis in rats. Materials and Methods: Cyclophosphamide (100 mg/kg) was injected to male Spraque-Dawley rats for cystitis induction. Animals were treated before and the day after cyclophosphamide injection with 100 mg/kg of nitric oxide substrate L-arginine, 20 mg/kg non-selective nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester, 20 mg/kg selective inducible nitric oxide synthase inhibitor S-methylisothiourea. Animals were exposured to hyperbaric oxygen (2.8 ATA for 90 minutes, twice daily) with or without 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 show meaningful protective effect. Hyperbaric oxygen protected the bladder against only ulceration. Moreover hyperbaric oxygen did not contribute to protective effects of L-arginine, L-NG-nitroarginine methyl ester and S-methylisothiourea. Conclusions: Nitric oxide produced by inducible nitric oxide synthase is an important mediator in the pathogenesis of cyclophosphamide-induced cystitis and hyperbaric oxygen has beneficial effect on repairing bladder damage rather than protection of bladder.