title: The Flaxseed-Derived Lignan Phenolic Secoisolariciresinol Diglucoside (SDG) Protects Non-Malignant Lung Cells from Radiation Damage.
abstract: Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS) has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed's protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG). SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR)-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1. Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure.
authors.affiliation: Department of Medicine, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, 3615 Civic Center Boulevard, Abramson Research Building, Suite 1016C, Philadelphia, PA 19104, USA. avela@mail.med.upenn.edu.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Velalopoulou
authors.affiliation: Department of Medicine, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, 3615 Civic Center Boulevard, Abramson Research Building, Suite 1016C, Philadelphia, PA 19104, USA. tyagisonia@gmail.com.
authors.forename: Sonia
authors.initials: S
authors.lastname: Tyagi
authors.affiliation: Department of Medicine, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, 3615 Civic Center Boulevard, Abramson Research Building, Suite 1016C, Philadelphia, PA 19104, USA. ralphp@mail.med.upenn.edu.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Pietrofesa
authors.affiliation: Department of Medicine, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, 3615 Civic Center Boulevard, Abramson Research Building, Suite 1016C, Philadelphia, PA 19104, USA. evguenia@mail.med.upenn.edu.
authors.forename: Evguenia
authors.initials: E
authors.lastname: Arguiri
authors.affiliation: Department of Medicine, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, 3615 Civic Center Boulevard, Abramson Research Building, Suite 1016C, Philadelphia, PA 19104, USA. melpo@mail.med.upenn.edu.
authors.forename: Melpo
authors.initials: M
authors.lastname: Christofidou-Solomidou
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002072:Butylene Glycols / Q000494:pharmacology*; D016923:Cell Death; D002478:Cells, Cultured; D004249:DNA Damage; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D019597:Flax / Q000737:chemistry*; D005720:Gamma Rays; D005960:Glucosides / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002072:Butylene Glycols; D005960:Glucosides; D005982:Glutathione Transferase; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); D010936:Plant Extracts; C491732:Nqo1 protein, mouse; C090142:secoisolariciresinol diglucoside
keywords: DNA damage; SDG; antioxidant; flaxseed; ionizing radiation; lignan; phenolic; radioprotection