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

Abstract

Although non-muscle invasive bladder cancer (NMIBC) is widely seen in men, most laboratory studies of new intravesical therapies to prevent NMIBC have been conducted on female animals. In addition, ozone (O 3 ) has been shown to be a beneficial agent as an intravesical application in the treatment of various disorders. In the current study, we evaluated the immunohistopathological and oxidative-antioxidative effects of intravesical O 3 treatment on n-methyl-n-nitrosourea (MNU)-induced NMIBC. Male Wistar-Albino rats (n=51) were divided into four groups: sham (n=6), O 3 only (n=15), MNU only (n=15), and MNU+O 3 (n=15). The MNU-only and MNU+O 3 groups received MNU, and the O 3 -only group received saline every other week for 10 weeks. The MNU-only group received 1 ml saline in place of O 3 treatment, whereas the O 3 -only and MNU+O 3 groups were treated with 1 ml 25 µg/ml O 3 between the 7th and 12th weeks. Rat bladders were collected in the 15th week for immunohistopathology and oxidant-antioxidant quantitation. Oxidant-antioxidant parameters were determined by ELISA. Although all surviving rats in the MNU-only group had preneoplastic (4/11, 36.4%) or neoplastic changes (7/11, 63.6%), a completely normal urothelium was observed in 2 rats (2/12, 16.7%) in the MNU+O 3 -group (P=0.478). More high-grade lesions were observed in the MNUonly group (4/11, 36.4%) than in the MNU+O 3 group (1/12, 8.3%) (P=0.120). All oxidant-antioxidant parameters significantly increased (P<0.05) in the O 3 -only group compared with the sham group. However, only antioxidant superoxide dismutase was remarkably higher (178.9%, P=0.060) in the MNU+O 3 group compared with the MNU-only group. This is the first methodologically and pathologically well-described male rat orthotopic bladder carcinogenesis model with intravesical MNU and administration of O 3 in NMIBC.

A Novel CpG Oligodeoxynucleotide Enhanced the Therapeutic Effect of Epirubicin on Bladder Tumors in Rats

“…The purpose of the present study was to further research the function of this CpG-ODN in a bladder cancer rat model and to explore its potential as a BCG replacement in clinical practice. MNU, a common chemical carcinogen [33], is usually used for the establishment of bladder cancer rat models [34,35].As the rat model can speci cally re ect the clinical characteristics, it is helpful in researching the instillation strategy for promoting bladder tumor onset [24]. In this study, the results of the rats with MNU instillation and 77.8% positive rate of bladder tumor onset indicated the successful establishment of a bladder cancer rat model.…”

Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer

“…Female SD rats were anesthetized using ether inhalation, and their bladders were infused using 0.2 ml N -methyl-Nnitrosurea (MNU) (10 mg/mL; Sigma, St. Louis, MO, USA,) using a 22-gage angiocatheter one every 14 days five times. After catheterization, the rats remained anesthetized for approximately 45 min to avoid spontaneous micturition [ 35 , 36 ].…”

Implantable orthotopic bladder cancer model in Wistar rats: A pilot and feasibility study

“…Moreover, we also compared this with other transplantable syngeneic rat BC models (Fischer 344,etc.). On the other hand, Satoh et al 2007) (10and Xiao et al (1999) (3) used 4x10 6 and 1 to 3x10 6 AY-27 cells in their Fischer 344 models, respectively. Using a higher concentration of NBT-II cells (>2x10 6 cells) or any immunosuppressive agent (steroid, etc.)…”

“…Taken together, it is evident that, immunocompetent orthotopical bladder tumor models are highly desirable for BC biology and immunology. Furthermore, the studies using chemically induced bladder carcinogenesis models require several months (5)(6)(7)(8). Hence, developing bladder tumors in a short time by implanting bladder cancer cell lines into the bladders of syngeneic immunocompetent ro-dents might be a valuable and practical option for the research of anticancer agents.…”