Hyperbaric oxygen therapy in a rat model of cyclophosphamide-induced hemorrhagic cystitis

To evaluate the effects of hyperbaric oxygen therapy (HBOT) on inflammation, oxidative stress, and bladder damage in a cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) rat model.

Forty male Wistar albino rats received a single intraperitoneal dose of 200 mg/kg CP to induce HC. Rats were assigned to either the HBOT or control groups and sacrificed on days 3, 7, and 14. The HBOT group received 6, 14, or 28 sessions of 100% oxygen at 2.4 ATA for 90 min. Outcomes included mortality, weight loss, bladder weight, macroscopic edema and hemorrhage scores, histopathology, Ki-67 immunostaining, and levels of cytokines (IL-1β, IL-4, IL-6, MCP-1, TNF-α) and malondialdehyde in bladder tissue, serum, and urine. Cytokines were quantified using the Luminex assay and malondialdehyde by ELISA.

Mortality and weight loss were similar between groups. On day 3, the HBOT group showed significantly lower bladder weights and hemorrhage scores (p < 0.01), with no significant differences in edema. On day 7, IL-1β and MCP-1 levels were higher in the HBOT group (p = 0.02). Malondialdehyde levels were significantly elevated in the control group on day 3. Histopathological and other cytokine findings showed no significant differences.

HBOT may provide early but transient benefits in alleviating HC based on macroscopic findings; however, these effects were not supported by sustained histopathological or molecular improvements. The high-dose CP model may have masked the potential therapeutic effects of HBOT. Further studies using lower or fractionated CP dosing and extended observation periods are warranted to better evaluate the therapeutic potential of HBOT.