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: Stephanie Puukila, Sean Bryan, Anna Laakso, Jessica Abdel-Malak, Carli Gurney, Adrian Agostino, Adriane Belló-Klein, Kailash Prasad, Neelam Khaper
• Journal: PloS one (PLoS One) Vol. 10 Issue 3 Pg. e0122852 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25822525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Butylene Glycols
• Cytokines
• FOXO3 protein, rat
• Forkhead Box Protein O3
• Forkhead Transcription Factors
• Glucosides
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Iron
• Superoxide Dismutase
• Ribosomal Protein S6 Kinases, 70-kDa
• AMP-Activated Protein Kinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• secoisolariciresinol diglucoside

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Apoptosis (drug effects)
• Butylene Glycols (pharmacology)
• Cell Line
• Cytokines (metabolism)
• Cytoprotection (drug effects)
• Forkhead Box Protein O3
• Forkhead Transcription Factors (metabolism)
• Gene Expression Regulation, Enzymologic (drug effects)
• Glucosides (pharmacology)
• Iron (metabolism, pharmacology)
• Matrix Metalloproteinase 2 (genetics)
• Matrix Metalloproteinase 9 (genetics)
• Myocytes, Cardiac (cytology, drug effects, metabolism)
• Oxidation-Reduction
• Oxidative Stress (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Superoxide Dismutase (metabolism)
• bcl-2-Associated X Protein (metabolism)