Peroxisome proliferator-activated receptor gamma agonist as a novel treatment for interstitial cystitis: A rat model.

PURPOSE

To understand the therapeutic potential of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist with a propensity to cause bladder mucosal proliferation, on interstitial cystitis (IC) in a rat model.

MATERIALS AND METHODS

Using a previously described animal model for IC, Sprague-Dawley rats were treated with biweekly cyclophosphamide injections (35 mg/kg) to induce cystitis. Animals were divided into 4 groups (n=6 for each group): IC plus daily sham saline gavage (ICPio), IC plus daily pioglitazone gavage (15 mg/kg) (ICPio), normal rats with daily pioglitazone (ICPio), and normal rats with neither IC nor pioglitazone (ICPio or Control). At the end of four weeks, urinary frequency and bladder capacity were measured. Histologic examination of urothelial integrity was also performed.

RESULTS

Average voids per hour were significantly lower in ICPio (4.0±1.9) vs. ICPio (10.0±2.4) rats (p<0.01) and were similar to ICPio (6.0±1.4) and ICPio (6.0±1.5) controls. Cystometric capacity was significantly higher in ICPio (0.945±0.122 mL) vs. ICPio rats (0.588±0.165 mL, p=0.01) and was comparable to ICPio capacity (0.817±0.196 mL) and ICPio capacity (0.941±0.188 mL). Urothelial structural integrity was improved in ICPio rats versus ICPio rats upon histologic observation.

CONCLUSIONS

Pioglitazone, a PPAR-γ agonist, improved bladder function in cyclophosphamide-induced cystitis by both observed urinary frequency and measured cystometric capacity. Urothelial structural integrity was also improved. Pioglitazone, due to a propensity to cause bladder mucosal proliferation, may prove useful for treating IC, and deserves further investigation.