The review included four recent preclinical studies (2023–2025), all demonstrating convergent evidence of ferroptotic features in animal models of experimental cystitis. Suppressed GPX4 and SLC7A11 expression, elevated malondialdehyde and lipid ROS levels, and disrupted antioxidant balance consistently marked the ferroptosis-prone bladder microenvironment. These findings were not only biochemically validated but also linked to histological deterioration and inflammatory signaling.
One of the most compelling insights was the therapeutic reversibility of ferroptotic damage. Iron chelators (e.g., dexrazoxane), natural antioxidants (pachymic acid), dietary interventions, and hydrogen sulfide donors were able to restore redox balance and attenuate bladder injury in experimental settings. Although none of the studies evaluated pain behavior or urodynamic profiles directly, the molecular rescue suggests clinical relevance.
From a translational perspective, we propose a conceptual model in which ferroptosis does not merely accompany bladder inflammation but perpetuates it, forming a feedback loop of oxidative damage, iron overload, and epithelial dysfunction. This mechanistic understanding opens the door for pathogenesis-based therapies, such as intravesical ferroptosis inhibitors or biomarker-guided intervention strategies. Of particular interest is the potential clinical use of GPX4, MDA, and SLC7A11 as noninvasive urinary biomarkers to monitor disease activity or therapeutic response.
While limited by the number and heterogeneity of available studies, our review provides a biologically coherent foundation for future investigation. Incorporating ferroptosis into IC/BPS research frameworks may enhance our ability to phenotype patients, stratify treatment, and identify novel therapeutic endpoints.
Written by: Bagrat Grigoryan,1,2 Victoria Kasyan,3 Michael Baboudjian,4 Olga Plekhanova,1 Dmitry Pushkar,1
- Moscow Urological Center, Botkin Hospital, Moscow, Russia.
- Urology Department of Russian University of Medicine, Botkin Hospital Moscow Urological Center, 2nd Botkinsky pr-d, 5, Moscow, 125284, Russian Federation.
- Department of Obstetrics, Gynecology, and Reproductive Medicine, Russian University of Medicine, Moscow, Russia.
- Department of Urology, North Academic Hospital, AP-HM, Marseille, France.