Redox Imbalance and NOS-Dependent Modulation of Superoxide in the Bladder Mucosa of Women With IC/BPS: A Preliminary...

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic condition characterized by bladder/pelvic pain and urinary symptoms, with poorly defined mechanisms and no reliable biomarkers. Oxidative stress, particularly reactive oxygen species (ROS), has been implicated in its pathophysiology, but direct human evidence remains scarce. Here, we evaluated ROS- and nitric oxide (NO)-related pathways in bladder mucosa from women with IC/BPS (n = 5) and controls (n = 7). Gene expression of NO-cGMP components, NADPH oxidases (NOX1-5), and antioxidant enzymes was assessed by qPCR. Baseline NO and superoxide ( $O_2^{-}$ ) levels were quantified using histochemical assays, and the effects of pharmacological inhibitors of NOS, iNOS and NOX enzymes were examined. IC/BPS samples displayed increased expression of PDE5A (3.1-fold) and p47phox (1.6-fold), along with reduced SOD1 expression (0.39-fold), consistent with an oxidative imbalance. Although baseline $O_2^{-}$ did not differ between groups, NOS inhibition with L-NAME markedly reduced $O_2^{-}$ generation, with a greater effect in IC/BPS tissue (85% reduction). Conversely, selective iNOS inhibition (1400 W) increased $O_2^{-}$ levels in IC/BPS biopsies. These findings suggest altered NOS-dependent redox regulation in the IC/BPS mucosa. Despite the limited sample size inherent to human biopsy studies, these results provide preliminary evidence of redox dysregulation in IC/BPS mucosa and highlight $O_2^{-}$ as a relevant mediator. They support further investigation into therapeutic strategies targeting NOS redox balance and cGMP signalling.