Comparison of Intravesical Hyaluronic Acid, Chondroitin Sulfate, and Combination of Hyaluronic Acid-Chondroitin Sulfate Therapies in Animal Model of Interstitial Cystitis

Abstract

Purpose: Three intravesical treatment agents were compared in an interstitial cystitis rat model: chondroitin sulfate, hyaluronic acid, and combined hyaluronic acid-chondroitin sulfate. Methods: Thirty-five female rats were divided into 5 groups: control (group I), isotonic (group II), chondroitin sulfate (group III), hyaluronic acid (group IV), and hyaluronic acid-chondroitin sulfate (group V). Chemical cystitis was induced in all experimental groups by intravesical instillation of 1 mL of hydrogen peroxide (H2O2) for 15 minutes via the transurethral route. The treatment was administered every other day for 3 sessions 2 days after inducing chemical cystitis. Groups II, III, IV, and V received 1 mL of 0.9% NaCl, 1 mL of 0.2% sodium chondroitin sulfate, 1 mL of low-molecular-weight hyaluronic acid, and 1 mL of 2% sodium chondroitin sulfate+ 1.6% sodium hyaluronic acid, respectively. On day 7, the animals were sacrificed and the bladders were removed for histopathological and immunohistochemical assessments. Results: Significant between-group differences were found in vascular congestion (P= 0.006). The grade of submucosal edema in groups II and IV was significantly higher than in group I (P= 0.006, P= 0.006, respectively). In group I, the grade of granulation tissue was lower than the other 4 groups, but no significant difference was found between the remaining groups (P= 0.016). Neutrophil cell infiltration was more intense in groups II and IV than in group I (P= 0.006, P= 0.006, respectively). Significant differences in the leukocyte and mast cell count were detected between groups II and IV (P< 0.001, P< 0.001, respectively). Abnormal zonula occludens-1 and uroplakin-III immunoreactivity in group II was higher than in groups I, III, or V (P= 0.002, P= 0.010, respectively). Interleukin-8 expression was lower in group V than in group II (P= 0.001). Conclusion: A single treatment of chondroitin sulfate and combined hyaluronic acid-chondroitin sulfate treatment demonstrated efficacy by suppressing inflammation and achieving improvements in the urothelium.