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Int J Exp Pathol ; 94(6): 362-72, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24205794

RESUMO

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.


Assuntos
Antioxidantes/uso terapêutico , Dieta , Metilnitrosoureia/efeitos adversos , Próstata/patologia , Doenças Prostáticas/induzido quimicamente , Doenças Prostáticas/prevenção & controle , gama-Tocoferol/uso terapêutico , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/patologia , Glutationa S-Transferase pi/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Próstata/efeitos dos fármacos , Próstata/metabolismo , Doenças Prostáticas/patologia , Ratos , Ratos Wistar , Receptores Androgênicos/metabolismo , gama-Tocoferol/administração & dosagem , gama-Tocoferol/farmacologia
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