Involvement of estrogen in the pathogenesis of cyclophosphamide-induced cystitis in rats

We examined the effects of ovariectomy and castration on the histology of cyclophosphamide (CP)-induced cystitis in rats. The animals were injected with CP (100 mg/kg) or saline intraperitoneally twice with an intervening 4 d and were euthanized at 1 or 2 wk after the initial CP administration. Saline treatment did not cause an apparent histological change in the bladder regardless of surgery, i.e., ovariectomy, castration, and sham-operation. CP treatment resulted in submucosal edema, urothelial damage, hemorrhage, and leukocyte infiltration in the bladder at 1 wk after the initial CP administration regardless of surgery. However, these histological changes were more severe in ovariectomized rats than in the sham-operated rats. In contrast, there were no significant differences in CP-induced histological changes in the bladder between castrated and sham-operated groups. We further examined the role of estrogen and progesterone on the CP-induced histology in the bladder by the replacement with estrogen only or estrogen plus progesterone for 2 wk in overiectomized rats. Estrogen treatment ameliorated CP-induced histological changes compared to oil treatment, whereas estrogen plus progesterone treatment did not produce any differences in the histology of the bladder compared to estrogen treatment. These results suggest that estrogen may play a role in the pathogenesis of bladder inflammation.