{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:37:30Z","timestamp":1790221050824,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,8,25]],"date-time":"2015-08-25T00:00:00Z","timestamp":1440460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Key Clinical Specialty Program","award":["No.: 2012-649"],"award-info":[{"award-number":["No.: 2012-649"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The present study aims to investigate the impacts and mechanisms of silymarin on paraquat (<jats:styled-content style=\"fixed-case\">PQ<\/jats:styled-content>)\u2010induced lung injury <jats:italic>in\u00a0vivo<\/jats:italic> and <jats:italic>in\u00a0vitro<\/jats:italic>. In <jats:italic>in\u00a0vivo<\/jats:italic> experiments, a total of 32 male Sprague\u2010Dawley (<jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>) rats were randomly divided into four groups. The rats were killed on day 3. Histopathological changes in lung tissue were examined using <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content> and Masson's trichrome staining. Biomarkers of neutrophil activation, pulmonary oedema, pulmonary fibrosis, lung permeability and oxidative stress were detected. Several proinflammatory mediators and antioxidant related proteins were measured. In <jats:italic>in\u00a0vitro<\/jats:italic> experiments, A549 cells were transfected with Nrf2 special si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> to investigate the roles of Nrf2. The results show that silymarin administration abated <jats:styled-content style=\"fixed-case\">PQ<\/jats:styled-content>\u2010induced lung histopathologic changes, decreased inflammatory cell infiltration and lung wet weight\/dry weight (W\/D) ratio, suppressed myeloperoxidase (<jats:styled-content style=\"fixed-case\">MPO<\/jats:styled-content>) activity and nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>)\/inducible nitric oxide synthases (<jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content>) expression, downregulated hydroxyproline (<jats:styled-content style=\"fixed-case\">HYP<\/jats:styled-content>) levels, reduced total protein concentration and proinflammatory mediator release, and improved oxidative stress (malondialdehyde, <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>; superoxide dismutase, <jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>; catalase, <jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>; and glutathione peroxidase, <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>\u2010Px) in lung tissue and serum. Meanwhile, treatment with silymarin upregulated the levels of nuclear factor\u2010erythroid\u20102\u2010related factor 2 (Nrf2), heme oxygenase\u20101 (<jats:styled-content style=\"fixed-case\">HO<\/jats:styled-content>\u20101) and <jats:styled-content style=\"fixed-case\">NAD<\/jats:styled-content>(P)H:quinone oxidoreductase\u20101(<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content>1). However, the addition of Nrf2 si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> reduced the expression of Nrf2\u2010mediated antioxidant protein <jats:styled-content style=\"fixed-case\">HO<\/jats:styled-content>\u20101 and thus reversed the protective effects of silymarin against oxidative stress and inflammatory response. These results suggest that silymarin may exert protective effects against <jats:styled-content style=\"fixed-case\">PQ<\/jats:styled-content>\u2010induced lung injury. Its mechanisms were associated with the Nrf2\u2010mediated pathway. Therefore, silymarin may be a potential therapeutic drug for lung injury.<\/jats:p>","DOI":"10.1111\/1440-1681.12448","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T17:39:31Z","timestamp":1436895571000},"page":"988-998","source":"Crossref","is-referenced-by-count":47,"title":["Silymarin attenuates paraquat\u2010induced lung injury via Nrf2\u2010mediated pathway <i>in\u00a0vivo<\/i> and <i>in\u00a0vitro<\/i>"],"prefix":"10.1111","volume":"42","author":[{"given":"Feng","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Shi","sequence":"additional","affiliation":[{"name":"Blood Purification Centre Shenyang Fourth People's Hospital Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiegang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhuo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,25]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"3392","article-title":"Toll\u2010like receptor 4 implicated in acute lung injury induced by paraquat poisoning in mice","volume":"7","author":"Liu W","year":"2014","journal-title":"Int. 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