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 (IC(+)Pio(−)), IC plus daily pioglitazone gavage (15 mg/kg) (IC(+)Pio(+)), normal rats with daily pioglitazone (IC(−)Pio(+)), and normal rats with neither IC nor pioglitazone (IC(−)Pio(−) 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 IC(+)Pio(+) (4.0±1.9) vs. IC(+)Pio(−) (10.0±2.4) rats (p<0.01) and were similar to IC(−)Pio(+) (6.0±1.4) and IC(−)Pio(−) (6.0±1.5) controls. Cystometric capacity was significantly higher in IC(+)Pio(+) (0.945±0.122 mL) vs. IC(+)Pio(−) rats (0.588±0.165 mL, p=0.01) and was comparable to IC(−)Pio(−) capacity (0.817±0.196 mL) and IC(−)Pio(+) capacity (0.941±0.188 mL). Urothelial structural integrity was improved in IC(+)Pio(+) rats versus IC(+)Pio(−) 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.