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LGM2605 is the synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2\u2212\/\u2212) mice. Cells were pretreated with LGM2605 (50 \u00b5M and 100 \u00b5M) and exposed to asbestos fibers (20 \u00b5g\/cm2) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1\u03b2 (IL-1\u03b2), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF\u03b1)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2\u2212\/\u2212 macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.<\/jats:p>","DOI":"10.3390\/antiox7030038","type":"journal-article","created":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T11:53:40Z","timestamp":1519991620000},"page":"38","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605) Reduces Asbestos-Induced Cytotoxicity in an Nrf2-Dependent and -Independent Manner"],"prefix":"10.3390","volume":"7","author":[{"given":"Ralph","family":"Pietrofesa","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shampa","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyewon","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evguenia","family":"Arguiri","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Albelda","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melpo","family":"Christofidou-Solomidou","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1158\/1078-0432.CCR-11-2259","article-title":"Molecular pathways: Targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma","volume":"18","author":"Carbone","year":"2012","journal-title":"Clin. 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