Investig Clin Urol.  2018 Jul;59(4):257-262. 10.4111/icu.2018.59.4.257.

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

• Mahal A
• Young-Lin
• Dobberfuhl A
• Estes J
• Comiter CV

• KMID: 2414759
• DOI: http://doi.org/10.4111/icu.2018.59.4.257

Abstract

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.

Keyword

Cystitis, interstitial; Pioglitazone; PPAR gamma

MeSH Terms

Animals
Cyclophosphamide
Cystitis
Cystitis, Interstitial*
Models, Animal*
Peroxisomes*
PPAR gamma*
Rats*
Rats, Sprague-Dawley
Urinary Bladder
Cyclophosphamide
PPAR gamma

Figure

• 

  Fig. 1 Cystometric volumes were averaged over three bladder fill cycles. Difference between mean volumes in IC+Pio− and IC+Pio+ were statistically significant p<0.01. IC, interstitial cystitis.

• 

  Fig. 2 Comparison of H&E (×40) from groups following 4 weeks treatment. (A) Normal staining is seen in the control (IC−Pio−). (B) A loss of normal urothelium and barrier thinning (arrows) is appreciated in the IC+Pio− group. (C) The IC−Pio+ group did not show significant changes from control. (D) The treated cystitis (IC+Pio+) group showed amelioration of the urothelium. IC, interstitial cystitis.

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