Simvastatin suppresses cyclophosphamide-induced changes in urodynamics and bladder inflammation.

Published

Journal Article

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. MATERIALS AND 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. CONCLUSION: 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.

Full Text

Duke Authors

Cited Authors

  • Hughes, FM; McKeithan, P; Ellett, J; Armeson, KE; Purves, JT

Published Date

  • January 2013

Published In

Volume / Issue

  • 81 / 1

Start / End Page

  • 209.e9 - 209.14

PubMed ID

  • 23153940

Pubmed Central ID

  • 23153940

Electronic International Standard Serial Number (EISSN)

  • 1527-9995

Digital Object Identifier (DOI)

  • 10.1016/j.urology.2012.08.041

Language

  • eng

Conference Location

  • United States