title: Dietary flaxseed enhances antioxidant defenses and is protective in a mouse model of lung ischemia-reperfusion injury.
abstract: Dietary flaxseed (FS) is a nutritional whole grain with high contents of omega-3 fatty acids and lignans with anti-inflammatory and antioxidant properties. We evaluated FS in a murine model of pulmonary ischemia-reperfusion injury (IRI) by dietary supplementation of 0% (control) or 10% (treatment) FS before IRI. Mice fed 0% FS undergoing IRI had a significant decrease in arterial oxygenation (Pa(O(2))) and a significant increase in bronchoalveolar lavage (BAL) protein compared with sham-operated mice. However, mice fed 10% FS undergoing IRI had a significant improvement in both Pa(O(2)) and BAL protein compared with mice fed 0% FS undergoing IRI. In addition, oxidative lung damage was decreased in 10% FS-supplemented mice undergoing IRI, as assessed by malondialdehyde levels. Immunohistochemical staining of lungs for iPF(2alpha)-III F(2) isoprostane, a measure of lipid oxidation, was diminished. FS-supplemented mice had less reactive oxygen species (ROS) release from the vascular endothelium in lungs in an ex vivo model of IRI, and alveolar macrophages isolated from FS-fed mice had significantly reduced ROS generation in response to oxidative burst. Pulmonary microvascular endothelial cells produced less ROS in a flow cessation model of ischemia when preincubated with purified FS lignan metabolites. Pharmacological inhibition of heme oxygenase-1 (HO-1) resulted in only a partial reduction of FS protection in the same model. We conclude that dietary FS is protective against IRI in an experimental murine model and that FS affects ROS generation and ROS detoxification via pathways not limited to upregulation of antioxidant enzymes such as HO-1.
authors: Department of Medicine, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors: James C
authors: JC
authors: Lee
authors: Faiz
authors: F
authors: Bhora
authors: Jing
authors: J
authors: Sun
authors: Guanjun
authors: G
authors: Cheng
authors: Evguenia
authors: E
authors: Arguiri
authors: Charalambos C
authors: CC
authors: Solomides
authors: Shampa
authors: S
authors: Chatterjee
authors: Melpo
authors: M
authors: Christofidou-Solomidou
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D019587:Dietary Supplements; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019597:Flax / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D017705:Lignans / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control*; D016897:Respiratory Burst / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D017705:Lignans; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D010100:Oxygen