{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T08:02:20Z","timestamp":1772697740147,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T00:00:00Z","timestamp":1408406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Associa\u00ef\u00bf\u00bd\u00ef\u00bf\u00bdo Portuguesa de Urologia","award":["Bolsa JABA RECORDATI Urologia 2010"],"award-info":[{"award-number":["Bolsa JABA RECORDATI Urologia 2010"]}]},{"name":"Portuguese Foundation for Science and Technology","award":["PTDC\/SAU-OSM\/65599\/2006"],"award-info":[{"award-number":["PTDC\/SAU-OSM\/65599\/2006"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Erectile dysfunction (<jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>) is a prevalent complication of diabetes, and oxidative stress is an important feature of diabetic <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>. Oxidative stress\u2010induced damage plays a pivotal role in the development of tissue alterations. However, the deleterious effects of oxidative stress in the corpus cavernosum with the progression of diabetes remain unclear. The aim of this study was to evaluate systemic and penile oxidative stress status in the early and late stages of diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>istar streptozotocin\u2010diabetic rats (and age\u2010matched controls) were examined 2 (early) and 8 weeks (late) after the induction of diabetes. Systemic oxidative stress was evaluated by urinary <jats:styled-content style=\"fixed-case\"><jats:roman>H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub><\/jats:roman><\/jats:styled-content> and the ratio of circulating reduced\/oxidized glutathione (<jats:styled-content style=\"fixed-case\">GSH\/GSSG<\/jats:styled-content>). Penile oxidative status was assessed by <jats:styled-content style=\"fixed-case\"><jats:roman>H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub><\/jats:roman><\/jats:styled-content> production and 3\u2010nitrotyrosine (3\u2010<jats:styled-content style=\"fixed-case\">NT<\/jats:styled-content>) formation. Cavernosal endothelial nitric oxide synthase (<jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>) was analyzed by quantitative immunohistochemistry. Dual immunofluorescence was also performed for 3\u2010<jats:styled-content style=\"fixed-case\">NT<\/jats:styled-content> and <jats:italic>\u03b1<\/jats:italic>\u2010smooth muscle actin (<jats:italic>\u03b1<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>\u2013<jats:italic>\u03b1<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a significant increase in urinary <jats:styled-content style=\"fixed-case\"><jats:roman>H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub><\/jats:roman><\/jats:styled-content> levels in both diabetic groups. The plasma <jats:styled-content style=\"fixed-case\">GSH\/GSSG<\/jats:styled-content> ratio was significantly augmented in late diabetes. In cavernosal tissue, <jats:styled-content style=\"fixed-case\"><jats:roman>H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub><\/jats:roman><\/jats:styled-content> production was significantly increased in late diabetes. Reactivity for 3\u2010<jats:styled-content style=\"fixed-case\">NT<\/jats:styled-content> was located predominantly in cavernosal smooth muscle (<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>) and was significantly reduced in late diabetes. Quantitative immunohistochemistry revealed a significant decrease in <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content> levels in cavernosal <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> and endothelium in late diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The findings indicate that the noxious effects of oxidative stress are more prominent in late diabetes. Increased penile protein oxidative modifications and decreased <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content> expression may be responsible for structural and\/or functional deregulation, contributing to the progression of diabetes\u2010associated <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.12181","type":"journal-article","created":{"date-parts":[[2014,6,9]],"date-time":"2014-06-09T11:23:06Z","timestamp":1402312986000},"page":"393-401","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Role of oxidative stress\u2010induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunction\u5728\u7cd6\u5c3f\u75c5\u6027\u52c3\u8d77\u529f\u80fd\u969c\u788d\u7684\u8fdb\u5c55\u8fc7\u7a0b\u4e2d\u6c27\u5316\u5e94\u6fc0\u6240\u8bf1\u5bfc\u7684\u5168\u8eab\u4ee5\u53ca\u6d77\u7ef5\u4f53\u5206\u5b50\u53d8\u5316\u7684\u5f71\u54cd"],"prefix":"10.1111","volume":"7","author":[{"given":"Angela","family":"Castela","sequence":"first","affiliation":[{"name":"Department of Biochemistry (U38\/FCT) Center for Medical Research Faculty of Medicine of the University of Porto  Porto Portugal"},{"name":"Institute for Molecular and Cell Biology of the University of Porto (IBMC\u2010UP)  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (U38\/FCT) Center for Medical Research Faculty of Medicine of the University of Porto  Porto Portugal"},{"name":"Department of Pharmacology and Therapeutics Center for Medical Research Faculty of Medicine of the University of Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina F.","family":"Domingues","sequence":"additional","affiliation":[{"name":"Requimte Instituto Superior de Engenharia Instituto Polit\u00e9cnico do Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Pa\u00edga","sequence":"additional","affiliation":[{"name":"Requimte Instituto Superior de Engenharia Instituto Polit\u00e9cnico do Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (U38\/FCT) Center for Medical Research Faculty of Medicine of the University of Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Vendeira","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Sa\u00fade Atl\u00e2ntica Cl\u00ednica Urol\u00f3gica Vendeira  Porto 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