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KMID : 1011820180590040257
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Investigative and Clinical Urology
2018 Volume.59 No. 4 p.257 ~ p.262
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Peroxisome proliferator-activated receptor gamma agonist as a novel treatment for interstitial cystitis: A rat model
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Mahal Amandeep
Young-Lin Nichole
Dobberfuhl Amy
Estes Jaclyn
Comiter Craig Vance
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Abstract
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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.
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KEYWORD
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Cystitis, interstitial, Pioglitazone, PPAR gamma
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