title: Preventive effect of intravesical ozone supplementation on n-methyl-n-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 (O3) 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 O3treatment on n-methyl-n-nitrosourea (MNU)-induced NMIBC. Male Wistar-Albino rats (n=51) were divided into four groups: sham (n=6), O3only (n=15), MNU only (n=15), and MNU+O3(n=15). The MNU-only and MNU+O3groups received MNU, and the O3-only group received saline every other week for 10 weeks. The MNU-only group received 1 ml saline in place of O3treatment, whereas the O3-only and MNU+O3groups were treated with 1 ml 25 µg/ml O3between 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+O3-group (P=0.478). More high-grade lesions were observed in the MNU-only group (4/11, 36.4%) than in the MNU+O3group (1/12, 8.3%) (P=0.120). All oxidant-antioxidant parameters significantly increased (P<0.05) in the O3-only group compared with the sham group. However, only antioxidant superoxide dismutase was remarkably higher (178.9%, P=0.060) in the MNU+O3group 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 O3in NMIBC.
authors.affiliation: Department of Urology, Kocaeli University School of Medicine, Eski İstanbul Yolu 10. Km., 41380, İzmit/Kocaeli, Turkey.
authors.forename: Kerem
authors.initials: K
authors.lastname: Teke
authors.affiliation: Department of Urology, Derince Training and Research Hospital, İbnisina Mahallesi, SSK Hst., 41900 Derince/Kocaeli, Turkey.
authors.forename: Tayyar A
authors.initials: TA
authors.lastname: Ozkan
authors.affiliation: Department of Urology, Derince Training and Research Hospital, İbnisina Mahallesi, SSK Hst., 41900 Derince/Kocaeli, Turkey.
authors.forename: Oguz O
authors.initials: OO
authors.lastname: Cebeci
authors.affiliation: Department of Urology, Kocaeli University School of Medicine, Eski İstanbul Yolu 10. Km., 41380, İzmit/Kocaeli, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Yilmaz
authors.affiliation: Department of Biochemistry, Kocaeli University School of Medicine, Eski İstanbul Yolu 10. Km., 41380, İzmit/Kocaeli, Turkey.
authors.forename: Muhammed E
authors.initials: ME
authors.lastname: Keles
authors.affiliation: Department of Urology, Kocaeli University School of Medicine, Eski İstanbul Yolu 10. Km., 41380, İzmit/Kocaeli, Turkey.
authors.forename: Levend
authors.initials: L
authors.lastname: Ozkan
authors.affiliation: Department of Biochemistry, Kocaeli University School of Medicine, Eski İstanbul Yolu 10. Km., 41380, İzmit/Kocaeli, Turkey.
authors.forename: Meltem O
authors.initials: MO
authors.lastname: Dillioglugil
authors.affiliation: Department of Pathology, Kocaeli University School of Medicine, Eski İstanbul Yolu 10. Km., 41380, İzmit/Kocaeli, Turkey.
authors.forename: Demir K
authors.initials: DK
authors.lastname: Yildiz
authors.affiliation: Department of Urology, Kocaeli University School of Medicine, Eski İstanbul Yolu 10. Km., 41380, İzmit/Kocaeli, Turkey.
authors.forename: Ozdal
authors.initials: O
authors.lastname: Dillioglugil
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008770:Methylnitrosourea / Q000009:adverse effects*; D010083:Oxidants, Photochemical / Q000008:administration & dosage*; D010126:Ozone / Q000008:administration & dosage*; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D010083:Oxidants, Photochemical; D010126:Ozone; D008770:Methylnitrosourea; D013482:Superoxide Dismutase
keywords: MNU; antioxidant response; bladder cancer model; intravesical ozone; male rat