title: Protective effect of γ-tocopherol-enriched diet on N-methyl-N-nitrosourea-induced epithelial dysplasia in rat ventral prostate.
abstract: Despite recent advances in understanding the biological basis of prostate cancer (PCa), the management of this disease remains a challenge. Chemoprotective agents have been used to protect against or eradicate prostate malignancies. Here, we investigated the protective effect of γ-tocopherol on N-methyl-N-nitrosourea (MNU)-induced epithelial dysplasia in the rat ventral prostate (VP). Thirty-two male Wistar rats were divided into four groups (n = 8): control (CT): healthy control animals fed a standard diet; control+γ-tocopherol (CT+γT): healthy control animals without intervention fed a γ-tocopherol-enriched diet (20 mg/kg); N-methyl-N-nitrosourea (MNU): rats that received a single dose of MNU (30 mg/kg) plus testosterone propionate (100 mg/kg) and were fed a standard diet; and MNU+γ-tocopherol (MNU+γT): rats that received the same treatment of MNU plus testosterone and were fed with a γ-tocopherol-enriched diet (20 mg/kg). After 4 months, the VPs were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase-2 (Cox-2), glutathione-S-transferase-pi (GST-pi) and androgen receptor (AR) protein expression, and matrix metalloproteinase-9 (MMP-9) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the MNU group was accompanied by augmented cell proliferation, GST-pi and Cox-2 immunoexpression and pro-MMP-9 activity. Stromal thickening and inflammatory foci were also observed. The administration of a γ-tocopherol-enriched diet significantly attenuated the adverse effects of MNU in the VP. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, GST-pi and Cox-2 immunoexpression. The gelatinolytic activity of pro-MMP-9 returned to the levels observed for the CT group. These results suggest that γ-tocopherol acts as a protective agent against MNU-induced prostatic disorders in the rat ventral prostate.
authors.affiliation: Department of Structural Biology, Institute of Biological and Natural Sciences, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil.
authors.forename: Lucas D
authors.initials: LD
authors.lastname: Sanches
authors.forename: Sergio A A
authors.initials: SA
authors.lastname: Santos
authors.forename: Jaqueline R
authors.initials: JR
authors.lastname: Carvalho
authors.forename: Gabriela D M
authors.initials: GD
authors.lastname: Jeronimo
authors.forename: Wagner J
authors.initials: WJ
authors.lastname: Favaro
authors.forename: Maria D G
authors.initials: MD
authors.lastname: Reis
authors.forename: Sérgio L
authors.initials: SL
authors.lastname: Felisbino
authors.forename: Luis A
authors.initials: LA
authors.lastname: Justulin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008770:Methylnitrosourea / Q000009:adverse effects*; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011469:Prostatic Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D024504:gamma-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D011944:Receptors, Androgen; D008770:Methylnitrosourea; D024504:gamma-Tocopherol; D051546:Cyclooxygenase 2; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat; D020780:Matrix Metalloproteinase 9
keywords: MMP-9; N-methyl-N-nitrosourea; cell proliferation; epithelial dysplasia; ventral prostate; γ-tocopherol