title: Simvastatin suppresses cyclophosphamide-induced changes in urodynamics and bladder inflammation.
abstract: OBJECTIVE
  To assess the ability of daily oral simvastatin administration to reduce the negative urodynamic changes associated with cyclophosphamide (CP)-induced cystitis and to prevent bladder inflammation. Patients undergoing CP chemotherapy frequently develop cystitis, leading to urinary dysfunction and hemorrhage. Recent studies have suggested statins possess anti-inflammatory properties and might be uroprotective.
  
  
  METHODS
  Urodynamic properties were analyzed in 4 groups of female Sprague-Dawley rats: group 1, vehicle (300 μL, 0.5% methylcellulose, orally for 7 days); group 2, simvastatin (1 mg/rat/d); group 3, vehicle plus CP (intraperitoneally 80 mg/kg, 24 h before cystometry); and group 4, simvastatin plus CP. The inflammation in the groups was assessed using Evans blue extravasation.
  
  
  RESULTS
  CP stimulated significant increases in the number of nonvoiding contractions (0.83±0.26 vs 4.97±1.90; P=.03) and decreases in the peak voiding pressure (53.46±5.08 vs 33.34±4.37 cm H2O; P=.01). Simvastatin returned these parameters to the control levels of 1.62±0.73 (P=.70) and 45.98±7.78 cm H2O (P=.38). CP at this level caused a slight, but significant, increase in the voided volume (0.82±0.13 vs 1.16±0.14 mL; P=.04), which returned to control levels (0.74±0.12 mL; P=.65) with simvastatin. Other urodynamic parameters, such as the threshold pressure, were not affected by simvastatin or CP, or the combination of the 2. CP-induced inflammation in the bladder (Evans blue extravasation) was suppressed by simvastatin.
  
  
  CONCLUSIONS
  Simvastatin was effective at ameliorating the negative urodynamic changes and inflammation in the bladder after CP administration and is a potential therapy for preventing side effects in patients undergoing this chemotherapy.
authors.affiliation: Department of Urology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Francis M
authors.initials: FM
authors.lastname: Hughes
authors.forename: Paige
authors.initials: P
authors.lastname: McKeithan
authors.forename: Justin
authors.initials: J
authors.lastname: Ellett
authors.forename: Kent E
authors.initials: KE
authors.lastname: Armeson
authors.forename: J Todd
authors.initials: JT
authors.lastname: Purves
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009119:Muscle Contraction / Q000187:drug effects; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D001743:Urinary Bladder / Q000187:drug effects; D014554:Urination / Q000187:drug effects; D014556:Urine; D014563:Urodynamics / Q000187:drug effects*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003520:Cyclophosphamide; D019821:Simvastatin