January 1, 2012 Human Health and Nutrition Data 0 Comments


Year: 2012
Authors: Lawrenz, J. Herndon, B. Kamal, A. Mehrer, A. Dim, D.C. Baidoo, C. Gasper, D. et. al.
Publication Name: Pulmonary Medicine
Publication Details: doi:10.1155/2012/457031


Bleomycin, a widely used antineoplastic agent, has been associated with severe pulmonary toxicity, primarily fibrosis. Previous work has shown a reduction in bleomycin-induced lung pathology by long-chain omega-3 fatty acids. Treatment by short chain omega3 fatty acids, alpha linolenic acid, found in dietary flaxseed oil may also reduce lung fibrosis, as previously evidenced in the kidney. To test this hypothesis, 72 rats were divided between diets receiving either 15% (w/w) flaxseed oil or 15% (w/w) corn oil (control). These groups were further divided to receive either bleomycin or vehicle (saline) via an oropharyngeal delivery, rather than the traditional intratracheal instillation. Lungs were harvested at 2, 7, and 21 days after bleomycin or saline treatment. Animals receiving flaxseed oil showed a delay in edema formation (P =  0.025) and a decrease in inflammatory cell infiltrate and vasculitis (P = 0.04 and 0.007, resp.). At days 7 and 21, bleomycin produced a reduction in pulmonary arterial lumen patency (P = 0.01), but not in rats that were treated with flaxseed oil. Bleomycin- treated rats receiving flaxseed oil had reduced pulmonary septal thickness (P = 0.01), signifying decreased fibrosis. Dietary flaxseed oil may prove beneficial against the side effects of this highly effective chemotherapeutic agent and its known toxic effects on the lung. (Authors abstract)

Bleomycin is a group of glycopeptides that binds iron and oxygen in vivo to produce an active drug, effective in cancer treatment. The chemotherapeutic mechanism results from the chelation of iron ions with oxygen, which leads to production of DNA-cleaving superoxide, and also hydroxide free radicals. It is the increased production of reactive oxygen species (ROS) that may be critical in producing  proinflammatory eicosanoids that lead to bleomycin�s pulmonary toxicity, and may eventually lead to lung fibrosis. A reduction in antioxidants has been reported in IPF lungs, and the resulting oxidant-antioxidant imbalance has been suggested in the progression of IPF (Idiopathic pulmonary fibrosis). Long chain omega3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have antioxidant properties and can protect against lung inflammation and pulmonary fibrosis. The omega 6 fatty acid, gamma linolenic acid (GLA) has also been shown to be a potent antioxidant and has been found to attenuate bleomycin induced lung fibrosis in hamsters. ALA from flaxseed oil protects against fibrosis in the kidney. The objective of this study was to determine the effect of ALA found in dietary flaxseed oil on bleomycin induced lung fibrosis. The results indicate that flaxseed oil was effective in  protecting lung tissue from bleomycin induced pulmonary toxicity in rats indicated by increased lumen patency and reduced pulmonary septal thickness, decreased inflammatory cell infiltrate, delayed edema formation, reduced vasculitis, and pulmonary and peribronchial fibrosis. ALA was found to be equally effective in protecting against fibrosis as long chain fatty acids. A potential mechanism to explain the anti inflammatory role of flaxseed oil involves lung eicosanoid production.  EPA and DHA eicosanoid derivatives are known to produce less active proinflammatory products than those of the typical omega 6 eicosanoid precursor, arachidonic acid. ALA derivatives have also been shown to have some anti-inflammatory action by competitively inhibiting the transformation of arachidonic acid to leukotrienes. ALA decreases production of the profibrotic PGE2 series. This study was able to show a protective effect of flaxseed oil against the bleomycin induced fibrosis within only a four week period of dietary treatment. This apparently provides sufficient time for the omega3 fatty acids to become incorporated into the phospholipid membranes. The four weeks of dietary treatment was half the length of time of dietary treatment that previously showed a protective effect of fish oil against the fibrosis. This difference in feeding time may have significant implications in considering testing the protective effects of omega3 fatty acids against fibrosis in the clinical setting. (Editors comments)

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