Effects of Ozone Therapy on Cyclophosphamide-induced Urinary Bladder Toxicity in Rats

Abstract

Purpose: is study investigated the e cacy of ozone therapy (OT) in a rat model of cyclophosphamide-induced hemorrhagic cystitis (HC).Methods: Forty Wistar Albino male rats were divided into ve 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. e CP+OT group received OT (0.2 mg/kg) i.p 24 h a er CP administration. CP was injected to the OT+CP group the day a er the third course of OT. All animals were killed four days a er CP administration. Bladder injury and oxidative stress parameters were determined from tissue samples.Results: We found small, but non-statistically signi cant 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 signi cant 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 e ects 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).Conclusion: OT prevented CP-induced urothelial damage by diminishing bladder oxidative stress, in ammation and NO levels. OT may help to ameliorate bladder damage induced by CP in the clinical setting.

Preventive effect of intravesical ozone supplementation on <i>n</i>-methyl-<i>n</i>-nitrosourea-induced non-muscle invasive bladder cancer in male rats

“…There has been considerable interest in researching the role of free radicals in carcinogenesis and the role of antioxidants in the prevention and treatment of cancer and related side effects [ 1 ]. The current study and that of Tasdemir et al [ 29 ] indicated that repeated low doses of O 3 application results in increased antioxidant response. In the current study, O 3 was used in a NMIBC treatment model for the first time.…”

“…O 3 has been described as one of the most oxidant agents at high levels (>80 µ g/ml) [ 2 ], but at low levels (20–25 µ g/ml), it is also known to have an antioxidant enhancing effect [ 28 ]. This is known as the paradoxal effect of O 3 [ 29 ]. The biphasic hormetic dose response may be useful for dual pharmacological effects generated by O 3 [ 3 ].…”

“…MPO is a lysosomal enzyme present both in neutrophils and monocytes. It also has a microbicidal effect and is a biochemical marker of inflammatory response [ 29 ]. MDA is a product of lipid peroxidation and exhibits cellular oxidative stress [ 28 , 29 ].…”

“…It also has a microbicidal effect and is a biochemical marker of inflammatory response [ 29 ]. MDA is a product of lipid peroxidation and exhibits cellular oxidative stress [ 28 , 29 ]. In the present study, GSH, NO, MPO, and MDA levels were significantly increased in the O 3 -only group compared with the sham group.…”

“…Ozone (O 3 ) creates a dose-related antioxidative-oxidative response in tissue [ 3 ] and has been used as a therapeutic agent for the treatment of tissue necrosis, peritonitis, infected wounds, chronic skin ulcers, burns, and advanced ischemic diseases with local or systemic administration [ 29 ]. On the other hand, O 3 has been shown to be beneficial as an intravesical agent in the treatment of bacterial [ 28 ], interstitial [ 16 ], and radiation cystitis [ 5 ] and has been shown to inhibit some cancer cells like breast and lung cancer cells in vitro [ 25 ].…”