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Am J Physiol Lung Cell Mol Physiol 294: L255-L265, 2008. First published December 14, 2007; doi:10.1152/ajplung.00138.2007
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Dietary flaxseed enhances antioxidant defenses and is protective in a mouse model of lung ischemia-reperfusion injury

James C. Lee,1,* Faiz Bhora,3,* Jing Sun,1 Guanjun Cheng,1 Evguenia Arguiri,1 Charalambos C. Solomides,4 Shampa Chatterjee,2 and Melpo Christofidou-Solomidou1

1Department of Medicine and 2Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; 3Division of Thoracic Surgery, Columbia University, New York, New York; and 4Department of Pathology, Temple University, Philadelphia, Pennsylvania

Submitted 6 April 2007 ; accepted in final form 10 December 2007

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 (PaO2) 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 PaO2 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 iPF2{alpha}-III F2 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.

lignans; nuclear factor-E2-related factor-2; heme oxygenase 1; phase II enzymes; ischemia-reperfusion injury


Address for reprint requests and other correspondence: M. Christofidou-Solomidou, Univ. of Pennsylvania, Dept. of Medicine, Pulmonary, Allergy and Critical Care Division, 3615 Civic Center Boulevard, Abramson Research Center, Office Suite 1016C, Philadelphia, PA 19104 (e-mail: melpo{at}mail.med.upenn.edu)






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