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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.
Highlights
Fruits, vegetables, cereals and beverages contain more than 8000 natural compounds that are characterized as polyphenols [1]
We incubated the three cell types with secoisolariciresinol diglucoside (SDG) (50 μM) and we evaluated the mRNA levels of heme oxygenase 1 (HO-1), GSTM1 and NQO1, at 1, 2, 4 and 6 h post SDG treatment, in all three cell types (epithelial, endothelial and fibroblasts (Figure 4)
We demonstrated for the first time that the lignan phenolic SDG can protect murine lung cells against radiation-induced oxidative damage
Summary
Vegetables, cereals and beverages contain more than 8000 natural compounds that are characterized as polyphenols [1]. The generation of reactive oxygen species (ROS) deregulates the endogenous antioxidant mechanisms in cells, leading to macromolecule damage, characterized in part by lipid peroxidation, DNA-protein crosslinks, base modifications, adduct formation and DNA single- and double-strand breaks [2,3]. These modifications initiate complex signal transduction pathways such as those involved in DNA repair, cell cycle arrest and induction of apoptosis [4]. Polyphenolic compounds can act as free radical scavengers and inhibitors of lipid peroxidation They upregulate pro-survival factors and cytoprotective antioxidant enzymes, as well as modulate DNA repair [6,9]
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