Acute acrolein-induced cystitis in mice

OBJECTIVE: To develop a method of direct intravesical administration of acrolein and evaluate the severity of cystitis in response to increasing doses of acrolein in female C57BL/6N (C57) mice, with further studies to compare the severity of acute acrolein-induced cystitis among C57, C3H/HeJ (HeJ), and C3H/OuJ (OuJ) strains of mice, as chemical cystitis produced by the systemic administration of cyclophosphamide is thought to result from renal excretion of hepatic metabolites, particularly acrolein. MATERIALS AND METHODS: Doses of acrolein (0-1000 microg, 15 microL total volume) were instilled into the bladders of C57 female mice; the bladders were removed 4 or 24 h later, weighed, and processed for histology. Acrolein (6 or 10 microg; 15 microL) was instilled into the bladders of C57, HeJ and OuJ female mice, the bladders removed 4 or 24 h later, weighed, and processed for standard histology and immunohistochemical detection of uroplakin. RESULTS: Increasing doses of acrolein up to 100-200 microg caused a linear increase in bladder weight and greater histological evidence of inflammation. Doses of >200 microg caused submaximal increases in bladder weight, apparently due to structural damage of the bladder. Bladder weight and submucosal oedema were consistently greater in C57 and HeJ than OuJ mice. Treatment with acrolein caused loss of urothelium along with uroplakin in some areas of all bladder sections 4 h after treatment. Bladders from C57 mice had some loss of urothelium 24 h after instillation of 6 or 10 microg acrolein, but urothelium and uroplakin covered nearly all the surface of bladders of HeJ and OuJ mice 24 h after treatment. There were significantly more white blood cells in bladders from C57 or HeJ mice than in bladders from OuJ mice 24 h after an instillation of 6 or 10 microg acrolein. CONCLUSIONS: Intravesical instillation of acrolein produces dose-dependent cystitis in mice. OuJ mice appear relatively more resistant to irritant effects of intravesical acrolein than C57 or HeJ mice, and future studies will be directed at identifying genetic causes for these differences.