Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic condition characterized by urinary urgency driven by pain or unpleasant sensations that are difficult to defer [1]. Damage to the glycosaminoglycan (GAG) layer is thought to contribute to symptom development, leading to widespread use of intravesical GAG replenishment in refractory patients. However, definitive alternative therapies are still needed [2]. This study aimed to investigate the histopathological and immunological effects of intravesical Tarantula Cubensis Extract (TCE) and Alpha-linolenic Acid (ALA), known for anti-inflammatory properties [3], in a chemical cystitis rat model, compared with standard intravesical Hyaluronic Acid (HA).

Forty female Wistar Albino rats were divided into five groups (n=8): control, chemical cystitis (CS), CS+ALA, CS+TCE, and CS+HA. CS was induced by intraperitoneal cyclophosphamide (50 mg/kg) administered three times at 3-day intervals. Controls received 0.9% NaCl.

Treatment groups received intravesical instillations twice weekly for two weeks: ALA (200 mg/kg in 2 mL saline), TCE (0.3 mL Theranekron, 1:100/D2), or HA (2 mL, 0.5%). Control and CS groups received saline instillations for comparable stress exposure. Rats were sacrificed three days after treatment completion, and cystectomy was performed.

Bladder tissues were divided for histopathological and ELISA analyses. Epithelial degeneration, fibrosis, submucosal edema, hyperemia, and inflammation were scored (0–3 scale). Mast cells were counted at 20× magnification. ELISA measured IL-6, SOD1, MDA, TNF-α, and NGF-β levels. Data were expressed as mean ± standard error. One-way ANOVA and LSD post hoc tests were used (SPSS v29).

Three rats died due to treatment-related side effects, leaving 37 animals for analysis.

The CS group showed significant increases in epithelial degeneration, submucosal edema, inflammation, and mast cell count compared to controls. Both CS+TCE and CS+HA groups demonstrated significant reductions in epithelial degeneration, fibrosis, submucosal edema, and mast cells, though hyperemia and inflammation scores remained unchanged. The CS+ALA group showed significant improvement in all parameters except hyperemia (Table 1).

Tissue MDA levels differed significantly among groups. The lowest MDA levels were observed in the CS+ALA group, significantly lower than CS+TCE and CS groups (p=0.006). No significant differences were found for other biomarkers (Table 2).

Model validity was confirmed by marked histopathological and inflammatory changes in the CS group. TCE and HA showed anti-inflammatory effects, while ALA demonstrated broader histological improvement and greater oxidative stress reduction.

Intravesical ALA demonstrated significant anti-inflammatory and tissue-protective effects in this preclinical IC/BPS model. These findings support its potential as an alternative intravesical therapy and warrant further clinical investigation.

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Continence 19S (2026) 102633
DOI: 10.1016/j.cont.2026.102633