title: Protective effect of simvastatin in the cyclophosphamide-induced hemorrhagic cystitis in rats.
abstract: OBJECTIVE
  Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP.
  
  
  METHODS
  Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9%. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-alpha, IL-1beta, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter.
  
  
  RESULTS
  In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-alpha, IL-1beta and IL-6 was significatly lower in CF/SINV rats (164.8 + or - 22, 44.8 + or - 8 and 52.4 + or - 13) than in CF/SAL rats (378.5 + or - 66, 122.9 + or - 26 e 123.6 + or - 18), respectively.
  
  
  CONCLUSIONS
  The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines.
authors.affiliation: Center of Experimental Surgery, Department of Surgery, Federal University of Rio Grande do Norte (UFRN), Natal-RN, Brazil.
authors.forename: Anna Carolina Batista
authors.initials: AC
authors.lastname: Dantas
authors.forename: Francisco Fábio de Araújo
authors.initials: FF
authors.lastname: Batista-Júnior
authors.forename: Larissa Freitas
authors.initials: LF
authors.lastname: Macedo
authors.forename: Mariana Noronha Castro
authors.initials: MN
authors.lastname: Mendes
authors.forename: Italo Medeiros
authors.initials: IM
authors.lastname: Azevedo
authors.forename: Aldo Cunha
authors.initials: AC
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000627:therapeutic use*; D014551:Urinary Tract / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D018906:Antineoplastic Agents, Alkylating; D016207:Cytokines; D003520:Cyclophosphamide; D019821:Simvastatin