| First Author | Pietrofesa RA | Year | 2018 |
| Journal | Antioxidants (Basel) | Volume | 7 |
| Issue | 3 | PubMed ID | 29498660 |
| Mgi Jnum | J:303416 | Mgi Id | MGI:6512169 |
| Doi | 10.3390/antiox7030038 | Citation | Pietrofesa RA, et al. (2018) Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605) Reduces Asbestos-Induced Cytotoxicity in an Nrf2-Dependent and -Independent Manner. Antioxidants (Basel) 7(3) |
| abstractText | Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. 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(-)/(-)) mice. Cells were pretreated with LGM2605 (50 microM and 100 microM) and exposed to asbestos fibers (20 microg/cm(2)) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1beta (IL-1beta), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha)), 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(-/-) 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. |
