Effects of ozone therapy on cyclophosphamide-induced urinary bladder toxicity in rats

This study investigated the efficacy of ozone therapy (OT) in a rat model of cyclophosphamide-induced hemorrhagic cystitis (HC).

Forty Wistar Albino male rats were divided into five groups: sham, OT, cyclophosphamide (CP), OT+CP and CP+OT. Hemorrhagic cystitis (HC) was induced by intraperitoneal (i.p) administration a single dose of 100 mg/kg CP. OT was performed once daily for three days. The CP+OT group received OT (0.2 mg/kg) i.p 24 h after CP administration. CP was injected to the OT+CP group the day after the third course of OT. All animals were killed four days after CP administration. Bladder injury and oxidative stress parameters were determined from tissue samples.

We found small, but non-statistically significant biochemical and histological changes in the animals treated with OT alone. CP administration induced cystitis, as manifested by a marked loss of urothelial cells, as well as hemorrhaging and edema in the bladder as determined by histopathological examination. It also caused a significant decrease in the endogenous antioxidant compound glutathione (GSH) and elevation of lipid peroxidation, and nitric oxide (NO) and myeloperoxidase (MPO) levels in the rats' urinary bladder tissue. OT was able to ameliorate these changes; however these effects were prominent in the CP+OT group when compared with the OT+CP group.: For example, the NO level in the CP+OT group was 68% of the OT+CP group (p < 0.05).

OT prevented CP-induced urothelial damage by diminishing bladder oxidative stress, inflammation and NO levels. OT may help to ameliorate bladder damage induced by CP in the clinical setting.