title: Involvement of estrogen in the pathogenesis of cyclophosphamide-induced cystitis in rats.
abstract: 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.
authors.affiliation: Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Michikazu
authors.initials: M
authors.lastname: Terado
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nomura
authors.forename: Kaori
authors.initials: K
authors.lastname: Mineta
authors.forename: Hisae
authors.initials: H
authors.lastname: Nishii
authors.forename: Naohiro
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Takakazu
authors.initials: T
authors.lastname: Sasaguri
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D002463:Cell Membrane Permeability / Q000187:drug effects; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D015914:Estrogen Replacement Therapy; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011374:Progesterone; D004958:Estradiol; D003520:Cyclophosphamide