title: Chemopreventive efficacy of Atorvastatin against nitrosamine-induced rat bladder cancer: antioxidant, anti-proliferative and anti-inflammatory properties.
abstract: To investigate the anti-carcinogenic effects of Atorvastatin (Atorva) on a rat bladder carcinogenesis model with N-butyl-N-(4-hydroxibutil)nitrosamine (BBN), four male Wistar rat groups were studied: (1) CONTROL: vehicle; (2) Atorva: 3 mg/kg bw/day; (3) Carcinogen: BBN (0.05%); (4) Preventive Atorva: 3 mg/kg bw/day Atorva + BBN. A two phase protocol was used, in which the drug and the carcinogen were given between week 1 and 8 and tumor development or chemoprevention were expressed between week 9 and 20, when the bladders were collected for macroscopic, histological and immunohistochemical (p53, ki67, CD31) evaluation. Serum was assessed for markers of inflammation, proliferation and redox status. The incidence of bladder carcinoma was: control 0/8 (0%); Atorva 0/8 (0%); BBN 13/20 (65%) and Atorva + BBN 1/8 (12.5%). The number and volume of tumors were significantly lower in the Atorva + BBN group, with a marked reduction in hyperplasia, dysplasia and carcinoma in situ lesions. An anti-proliferative, anti-inflammatory and antioxidant profile was also observed in the preventive Atorva group. p53 and ki67 immunostaining were significantly increased in the BBN-treated rats, which was prevented in the Atorva + BBN group. No differences were found for CD31 expression. In conclusion, Atorvastatin had a clear inhibitory effect on bladder cancer development, probably due to its antioxidant, anti-proliferative and anti-inflammatory properties.
authors.affiliation: Laboratory of Pharmacology & Experimental Therapeutics, Institute of Biomedical Research on Light and Image, Medicine Faculty, Coimbra University, Coimbra, 3000-548, Portugal.|Department of Urology & Renal Transplantation, Coimbra University Hospital, Coimbra, 3000-075, Portugal.
authors.forename: Belmiro
authors.initials: B
authors.lastname: Parada
authors.affiliation: Laboratory of Pharmacology & Experimental Therapeutics, Institute of Biomedical Research on Light and Image, Medicine Faculty, Coimbra University, Coimbra, 3000-548, Portugal.
authors.forename: Flávio
authors.initials: F
authors.lastname: Reis
authors.affiliation: Laboratory of Pharmacology & Experimental Therapeutics, Institute of Biomedical Research on Light and Image, Medicine Faculty, Coimbra University, Coimbra, 3000-548, Portugal.
authors.forename: Ângela
authors.initials: Â
authors.lastname: Pinto
authors.affiliation: Laboratory of Pharmacology & Experimental Therapeutics, Institute of Biomedical Research on Light and Image, Medicine Faculty, Coimbra University, Coimbra, 3000-548, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Sereno
authors.affiliation: Service of Anatomic Pathology, Coimbra University Hospital, Coimbra, 3000-075, Portugal.
authors.forename: Maria
authors.initials: M
authors.lastname: Xavier-Cunha
authors.affiliation: Service of Anatomic Pathology, Coimbra University Hospital, Coimbra, 3000-075, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Neto
authors.affiliation: Research Centre for Health Sciences, Beira Interior University, Covilhã, 6201-506, Portugal.
authors.forename: Petronila
authors.initials: P
authors.lastname: Rocha-Pereira
authors.affiliation: Department of Urology & Renal Transplantation, Coimbra University Hospital, Coimbra, 3000-075, Portugal.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mota
authors.affiliation: Department of Urology & Renal Transplantation, Coimbra University Hospital, Coimbra, 3000-075, Portugal.
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Figueiredo
authors.affiliation: Laboratory of Pharmacology & Experimental Therapeutics, Institute of Biomedical Research on Light and Image, Medicine Faculty, Coimbra University, Coimbra, 3000-548, Portugal.
authors.forename: Frederico
authors.initials: F
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D014408:Biomarkers, Tumor / Q000097:blood; D002085:Butylhydroxybutylnitrosamine; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018384:Oxidative Stress; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D014408:Biomarkers, Tumor; D006538:Heptanoic Acids; D011758:Pyrroles; D002085:Butylhydroxybutylnitrosamine; D000069059:Atorvastatin