Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disorder with a poorly understood etiology and limited therapeutic options. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been implicated in bladder epithelial damage, suggesting a potential role in IC/BPS pathogenesis.
To systematically review available preclinical studies examining the potential role of ferroptosis in experimental models relevant to interstitial cystitis, with a focus on molecular mechanisms and ferroptosis-related biomarkers.
This systematic review was conducted in accordance with the PRISMA 2020 guidelines. A structured PICO framework was used to identify eligible preclinical studies that evaluated ferroptosis in animal models or ex vivo systems mimicking interstitial cystitis. Data were extracted regarding ferroptosis markers, signaling pathways, and therapeutic interventions.
Four preclinical studies were included, involving rodent models of cyclophosphamide- and LPS-induced cystitis, cystitis glandularis, and one study incorporating human bladder biopsies. Across all studies, ferroptosis was consistently associated with bladder injury, characterized by decreased expression of GPX4 and SLC7A11, elevated malondialdehyde (MDA), and increased lipid ROS. Key regulatory pathways involved included Wnt/β-catenin, NF-κB, and Nrf2. Ferroptosis inhibitors such as dexrazoxane, hydrogen sulfide donors, dietary restriction, and pachymic acid attenuated bladder damage by restoring redox homeostasis. None of the studies evaluated pain-related outcomes or functional bladder parameters, which limits the translational interpretation of findings in the context of IC/BPS symptomatology.
This systematic review highlights ferroptosis as a compelling mechanistic link between chronic inflammation and urothelial injury in interstitial cystitis/bladder pain syndrome. Targeting ferroptosis may offer a novel disease-modifying strategy in a condition where current treatments remain largely symptomatic. Future translation into clinical settings could involve biomarker-guided phenotyping and intravesical delivery of ferroptosis-modulating agents to achieve localized and pathogenesis-based therapy. However, given the limited number of studies and the lack of human validation, these findings should be considered preliminary and hypothesis-generating.
International urology and nephrology. 2026 Apr 18 [Epub ahead of print]
Bagrat Grigoryan, Victoria Kasyan, Michael Baboudjian, Olga Plekhanova, Dmitry Pushkar
Moscow Urological Center, Botkin Hospital, Moscow, Russia. ., Department of Obstetrics, Gynecology, and Reproductive Medicine, Russian University of Medicine, Moscow, Russia., Department of Urology, North Academic Hospital, AP-HM, Marseille, France., Moscow Urological Center, Botkin Hospital, Moscow, Russia.