Involvement of Interleukin-6-Regulated Nitric Oxide Synthase in Hemorrhagic Cystitis and Impaired Bladder Contractions in Young Rats Induced by Acrolein, a Urinary Metabolite of Cyclophosphamide

摘要: Hemorrhagic cystitis is a common complication in children receiving cyclophosphamide, chemotherapeutic alkylating agent. Acrolein urinary metabolite from cyclophosphamide and can induce hemorrhagic cystitis. Here, we investigated the effects mechanisms of acrolein by intravesical instillation on bladder muscle contractions pathological alterations rats. significantly increased rat detrusor after 1 6 h but markedly decreased 24 h. phosphorylated protein kinase C (pan-PKC) expressions bladders inhibited it Inducible nitric oxide (NO) synthase (iNOS) were induced treatment. Twenty-four-hour levels nitrite/nitrate interleukin-6 (IL-6) bladder. The iNOS inhibitors acrolein-increased levels, not IL-6 levels. IL-6-neutralizing antibodies effectively NOx 1-h treatment reversed PKC inhibitor RO32-0432, 24-h antibody. Both antibody expression, phosphorylation, weight, rats Taken together, these results suggest that an IL-6-regulated iNOS/NO signaling pathway participates acrolein-triggered contraction inhibition These findings may help us to find new strategy treat cyclophosphamide-induced