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Resolvin E1 (RvE1) is a representative member of the eicosapentaenoic omega-3 lipid derivatives, and is a drug candidate of the growing family of endogenous resolvins. Considering the aforementioned, the main objective of this study was to analyze the hepatoprotective effect of RvE1 in a rat model of liver fibrosis. Male Sprague-Dawley rats received diethylnitrosamine (DEN, 70 mg\/mg body weight intraperitoneally (i.p)) as an inductor of liver fibrosis once weekly and RvE1(100 ng\/body weight i.p) twice weekly for four weeks. RvE1 suppressed the alterations induced by DEN, normalizing the levels of alanine aminotransferase (ALT), albumin, and lactate dehydrogenase (LDH), and ameliorated DEN injury by decreasing the architecture distortion, inflammatory infiltration, necrotic areas, and microsteatosis. RvE1 also limited DEN-induced proliferation through a decrease in Ki67-positive cells and cyclin D1 protein expression, which is related to an increase of the levels of cleaved caspase-3. Interestingly, we found that RvE1 promotes higher nuclear translocation of nuclear factor \u03baB (NF-\u03baB)p65 than DEN. RvE1 also increased the levels of nuclear the nuclear factor erythroid 2\u2013related factor 2 (Nrf2), but with no antioxidant effect, measured as an increase in glutathione disulfide (GSSG) and a decrease in the ratio of glutathione (GSH)\/GSSG. Taken together, these results suggest that RvE1 modulates the fibrogenesis, steatosis, and cell proliferation in a model of DEN induced fibrosis.<\/jats:p>","DOI":"10.3390\/ijms21228827","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T01:28:48Z","timestamp":1606094928000},"page":"8827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Pro-Resolving Lipid Mediator Resolvin E1 Mitigates the Progress of Diethylnitrosamine-Induced Liver Fibrosis in Sprague-Dawley Rats by Attenuating Fibrogenesis and Restricting Proliferation"],"prefix":"10.3390","volume":"21","author":[{"given":"Maria Jos\u00e9","family":"Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas Biom\u00e9dicas, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile"},{"name":"Programa de Doctorado en Ciencias Menci\u00f3n Investigaci\u00f3n y Desarrollo de Productos Bioactivos, Instituto de Qu\u00edmica de los Recursos Naturales, Universidad de Talca, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Herrera","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas Biom\u00e9dicas, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Donoso","sequence":"additional","affiliation":[{"name":"Departamento de Estomatolog\u00eda, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Castillo","sequence":"additional","affiliation":[{"name":"Unidad de Anatom\u00eda Patol\u00f3gica, Hospital Regional de Talca, Talca 3460001, Chile"},{"name":"Centro Oncol\u00f3gico, Facultad de Medicina, Universidad Cat\u00f3lica del Maule, Talca 3466706, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Orrego","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica e Inmunohematolog\u00eda, Facultad Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3437-8998","authenticated-orcid":false,"given":"Daniel R.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas Biom\u00e9dicas, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-991X","authenticated-orcid":false,"given":"Jessica","family":"Z\u00fa\u00f1iga-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas Biom\u00e9dicas, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.jep.2009.01.035","article-title":"Protective effects of astragaloside IV on porcine-serum-induced hepatic fibrosis in rats and in vitro effects on hepatic stellate cells","volume":"122","author":"Liu","year":"2009","journal-title":"J. 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