{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:31:37Z","timestamp":1773279097660,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T00:00:00Z","timestamp":1383004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Experimental Path"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Despite recent advances in understanding the biological basis of\u00a0prostate cancer (<jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>a), the management of this disease remains a challenge. Chemoprotective agents have been used\u00a0to protect against or eradicate\u00a0prostate\u00a0malignancies. Here, we investigated the protective effect of \u03b3\u2010tocopherol on <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (<jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content>)\u2010induced epithelial dysplasia in the rat ventral prostate (<jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>). Thirty\u2010two male Wistar rats were divided into four groups (<jats:italic>n<\/jats:italic>\u00a0=\u00a08): control (<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>): healthy control animals fed a standard diet; control+\u03b3\u2010tocopherol (<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>+\u03b3T): healthy control animals without intervention fed a \u03b3\u2010tocopherol\u2010enriched diet (20\u00a0mg\/kg); <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (<jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content>): rats that received a single dose of <jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content> (30\u00a0mg\/kg) plus testosterone propionate (100\u00a0mg\/kg) and were fed a standard diet; and <jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content>+\u03b3\u2010tocopherol (<jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content>+\u03b3T): rats that received the same treatment of <jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content> plus testosterone and were fed with a \u03b3\u2010tocopherol\u2010enriched diet (20\u00a0mg\/kg). After 4\u00a0months, the <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>s were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase\u20102 (Cox\u20102), glutathione\u2010S\u2010transferase\u2010pi (<jats:styled-content style=\"fixed-case\">GST<\/jats:styled-content>\u2010pi) and androgen receptor (<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>) protein expression, and matrix metalloproteinase\u20109 (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the <jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content> group was accompanied by augmented cell proliferation, <jats:styled-content style=\"fixed-case\">GST<\/jats:styled-content>\u2010pi and Cox\u20102 immunoexpression and pro\u2010<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109 activity. Stromal thickening and inflammatory foci were also observed. The administration of a \u03b3\u2010tocopherol\u2010enriched diet significantly attenuated the adverse effects of <jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content> in the <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, <jats:styled-content style=\"fixed-case\">GST<\/jats:styled-content>\u2010pi and Cox\u20102 immunoexpression. The gelatinolytic activity of pro\u2010<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109 returned to the levels observed for the <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> group. These results suggest that \u03b3\u2010tocopherol acts as a protective agent against <jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content>\u2010induced prostatic disorders in the rat ventral prostate.<\/jats:p>","DOI":"10.1111\/iep.12042","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T04:40:42Z","timestamp":1383021642000},"page":"362-372","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Protective effect of \u03b3\u2010tocopherol\u2010enriched diet on <i>N<\/i>\u2010methyl\u2010<i>N<\/i>\u2010nitrosourea\u2010induced epithelial dysplasia in rat ventral prostate"],"prefix":"10.1111","volume":"94","author":[{"given":"Lucas D.","family":"Sanches","sequence":"first","affiliation":[{"name":"Department of Structural Biology Institute of Biological and Natural Sciences Federal University of Triangulo Mineiro Uberaba MG Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio A. A.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Morphology Institute of Bioscience Univ Estadual Paulista Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaqueline R.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Morphology Institute of Bioscience Univ Estadual Paulista Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela D. M.","family":"Jeronimo","sequence":"additional","affiliation":[{"name":"Department of Structural Biology Institute of Biological and Natural Sciences Federal University of Triangulo Mineiro Uberaba MG Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wagner J.","family":"Favaro","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology Institute of Biology University of Campinas\u2010UNICAMP Campinas SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria D. G.","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of Structural Biology Institute of Biological and Natural Sciences Federal University of Triangulo Mineiro Uberaba MG Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9rgio L.","family":"Felisbino","sequence":"additional","affiliation":[{"name":"Department of Morphology Institute of Bioscience Univ Estadual Paulista Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Luis A.","family":"Justulin","sequence":"additional","affiliation":[{"name":"Department of Structural Biology Institute of Biological and Natural Sciences Federal University of Triangulo Mineiro Uberaba MG Brazil"},{"name":"Department of Morphology Institute of Bioscience Univ Estadual Paulista Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,10,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2011.010392"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24106"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00817-6"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-8428(03)00042-8"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635580902825654"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.02.007"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-9-241"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)65248-0"},{"key":"e_1_2_6_10_1","first-page":"251","article-title":"Stromal\u2010epithelial interactions in normal and abnormal prostatic development","volume":"239","author":"Cunha G.R.","year":"1987","journal-title":"Prog. Clin. Biol. Res."},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65517-4"},{"key":"e_1_2_6_12_1","first-page":"240","article-title":"Quantitative determination of prostatic epithelial and stromal hyperplasia by a new technique biomorphometrics","volume":"16","author":"DeKlerk D.P.","year":"1978","journal-title":"Invest. Urol."},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2009.09.017"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-40901-4_4"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-11-0521"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0045(20000901)44:4<287::AID-PROS5>3.0.CO;2-Z"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540214315"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2003.10.009"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.200357097"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/74.6.714"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1331.056"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e31821b59c6"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01002772"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2007.03.008"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/10520295.2012.724713"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.4111\/kju.2011.52.4.253"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1437"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601910379132"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2010.46.12.1537942"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.10.4816"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(96)90396-2"},{"key":"e_1_2_6_32_1","first-page":"2089","article-title":"Increased cyclooxygenase\u20102 expression in human squamous cell carcinomas of the head and neck and inhibition of proliferation by nonsteroidal anti\u2010inflammatory drugs","volume":"22","author":"Lee D.W.","year":"2002","journal-title":"Anticancer Res."},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.10.1701"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010423"},{"key":"e_1_2_6_35_1","first-page":"4245","article-title":"NS398, a selective cyclooxygenase\u20102 inhibitor, induces apoptosis and down\u2010regulates bcl\u20102 expression in LNCaP cells","volume":"58","author":"Liu X.H.","year":"1998","journal-title":"Cancer Res."},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp332"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20862"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0045(199602)28:2<124::AID-PROS8>3.0.CO;2-G"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.69.6.851"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.1115"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000047364.56051.74"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2013.02.007"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2613.2012.00843.x"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-0946"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.21886"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ucl.2009.11.003"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOU.0b013e3283381966"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0942"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20915"},{"issue":"7","key":"e_1_2_6_50_1","first-page":"S10","article-title":"Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP\u20107 during epithelial\u2010to\u2010mesenchymal transition","volume":"94","author":"Tasanarong A.","year":"2011","journal-title":"J. Med. Assoc. Thai."},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.12.027"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-012-1278-y"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.27.061406.093819"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2004.02.004"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0045(20000615)44:1<31::AID-PROS5>3.0.CO;2-O"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-12-0045"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejcn.1602154"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207435"}],"container-title":["International Journal of Experimental Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fiep.12042","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iep.12042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T10:02:25Z","timestamp":1696327345000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iep.12042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,29]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["10.1111\/iep.12042"],"URL":"https:\/\/doi.org\/10.1111\/iep.12042","archive":["Portico"],"relation":{},"ISSN":["0959-9673","1365-2613"],"issn-type":[{"value":"0959-9673","type":"print"},{"value":"1365-2613","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,29]]},"assertion":[{"value":"2013-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-10-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}