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Silymarin (SIL) is a hepatoprotective and antioxidant medicament largely prescribed against liver diseases that has previously been shown to prevent fibrosis during acute murine schistosomiasis. Here we employed silymarin to try to reverse established hepatic fibrosis in chronic schistosomiasis. Silymarin or vehicle was administered to BALB\/c mice every 48 h, starting on the 40th (80 days of treatment), 70th (50 days), or 110th (10 days) day postinfection (dpi). All mice were sacrificed and analyzed at 120 dpi. Treatment with silymarin reduced liver weight and granuloma sizes, reduced the increase in alanine aminotransferase and aspartate aminotransferase levels, and reduced the established hepatic fibrosis (assessed by hydroxyproline contents and picrosirius staining). Treatment with silymarin also reduced the levels of interleukin-13 (IL-13) in serum and increased the gamma interferon (IFN-\u03b3)\/IL-13 ratio. There was a linear correlation between IL-13 levels in serum and hydroxyproline hepatic content in both infected untreated and SIL-treated mice, with decreased IL-13 levels corresponding to decreased hydroxyproline hepatic contents. Treatment with either SIL or N-acetylcysteine reduced both proliferation of fibroblast cell lines and basal\/IL-13-induced production of collagen I, indicating that besides inhibiting IL-13 production during infection, SIL antioxidant properties most likely contribute to inhibition of collagen production downstream of IL-13. These results show that silymarin interferes with fibrogenic cytokines, reduces established fibrosis, and inhibits downstream effects of IL-13 on fibrogenesis, indicating the drug as a safe and cheap treatment to liver fibrotic disease in schistosomiasis.<\/jats:p>","DOI":"10.1128\/aac.01936-13","type":"journal-article","created":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T03:59:58Z","timestamp":1390363198000},"page":"2076-2083","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Silymarin Reduces Profibrogenic Cytokines and Reverses Hepatic Fibrosis in Chronic Murine Schistosomiasis"],"prefix":"10.1128","volume":"58","author":[{"given":"H\u00edlton Ant\u00f4nio","family":"Mata-Santos","sequence":"first","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Farm\u00e1cia, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabianno Ferreira","family":"Dutra","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Microbiologia Prof. Paulo de G\u00f3es, Departamento de Imunologia, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Carneiro","family":"Rocha","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Farm\u00e1cia, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana Gon\u00e7alves","family":"Lino","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Farm\u00e1cia, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola Ramos","family":"Xavier","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Farm\u00e1cia, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro Andrade","family":"Chinalia","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Microbiologia Prof. Paulo de G\u00f3es, Departamento de Imunologia, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan Hudson","family":"Hossy","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Farm\u00e1cia, Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgana Teixeira Lima","family":"Castelo-Branco","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Ci\u00eancias Biom\u00e9dicas, Programa de Pesquisa em Glicobiologia, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson Junger","family":"Teodoro","sequence":"additional","affiliation":[{"name":"Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Programa de P\u00f3s-gradua\u00e7\u00e3o de Alimentos e Nutri\u00e7\u00e3o, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia N.","family":"Paiva","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Microbiologia Prof. Paulo de G\u00f3es, Departamento de Imunologia, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre dos Santos","family":"Pyrrho","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Farm\u00e1cia, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(06)70521-7"},{"key":"e_1_3_2_3_2","first-page":"1","article-title":"Action against worms","volume":"1","author":"World Health Organization","year":"2003","unstructured":"World Health Organization. 2003. 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