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

Teke K., Ozkan T. A., Cebeci O. O., YILMAZ H., Keles M. E., Ozkan L., ...More

EXPERIMENTAL ANIMALS, vol.66, no.3, pp.191-198, 2017 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 66 Issue: 3
  • Publication Date: 2017
  • Doi Number: 10.1538/expanim.16-0093
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.191-198
  • Keywords: antioxidant response, bladder cancer model, intravesical ozone, male rat, MNU, FEMALE MICE, THERAPY, MODEL, CATHETERIZATION, INDUCTION, APOPTOSIS, GROWTH, CELLS, RISK
  • Kocaeli University Affiliated: Yes


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+O3 (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 pg/nnl 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.