title: Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.
abstract: Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Puukila
authors.affiliation: Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Sean
authors.initials: S
authors.lastname: Bryan
authors.affiliation: Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Laakso
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Abdel-Malak
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Carli
authors.initials: C
authors.lastname: Gurney
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Agostino
authors.affiliation: Department of Physiology, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Adriane
authors.initials: A
authors.lastname: Belló-Klein
authors.affiliation: Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Kailash
authors.initials: K
authors.lastname: Prasad
authors.affiliation: Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Neelam
authors.initials: N
authors.lastname: Khaper
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002072:Butylene Glycols / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D002072:Butylene Glycols; D016207:Cytokines; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D005960:Glucosides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D007501:Iron; D013482:Superoxide Dismutase; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D055372:AMP-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C090142:secoisolariciresinol diglucoside
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