Dietary Flaxseed Oil Protects against Bleomycin-Induced Pulmonary Fibrosis in Rats

Abstract

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 omega-3 fatty acids, α-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.

Therapeutic effect of flaxseed oil on experimental pulmonary fibrosis induced by bleomycin in rats

“…FO enriched in PUFA (ALA) and phytoestrogenic lignans provide one such dietary source of biologically active components that has been shown to be co-preventive 20 and co-therapeutic 10 in a wide variety of ailments. The two main fatty acids, linoleic and alpha linolenic acid, are like vitamins: we cannot make them.…”

Modulatory effects of green tea and aloe vera extracts on experimentally-induced lung fibrosis in rats: histological and immunohistochemical study

“…Other researcher reported that bleomycin increases lung epithelial cell apoptosis in a reactive oxygen species (ROS)-dependent manner [28]. BLM-induced pulmonary fibrosis was explained by some authors who reported that the chemotherapeutic mechanism of BLM results from the chelation of iron ions with oxygen, which leads to production of DNA-cleaving superoxide, and also hydroxide free radicals [29]. It is the increased production of ROS that lead to bleomycin's pulmonary toxicity, and may eventually lead to lung fibrosis.…”

Insights into the Role of Bioactive Food Ingredients and the Microbiome in Idiopathic Pulmonary Fibrosis

“…The supplementation of the diet with flaxseeds triggers anti-fibrotic effects, both before and after lung damage [ 128 , 129 ], doubling the survival rate when analysed as a therapeutic agent. When flaxseeds are given as oil, this treatment also reduces lung damage, as previously mentioned, an effect that is attributed to their high short-chain ω-3 PUFA content [ 51 , 52 ]. However, it has been demonstrated that lignans from wholegrain flaxseed decrease inflammation, lung injury and eventual fibrosis while it improves survival after radiation exposure, evidencing that it is a bioactive component responsible for lung damage mitigation [ 130 ].…”

“…In the context of lung fibrosis, a relevant example of the importance of dietary lipids in the perinatal period for the development of diseases in adulthood comes from an experiment in which maternal diet supplementation with docosahexaenoic acid attenuated pulmonary fibrosis and improved lung function in mouse pups exposed to perinatal inflammation [ 49 ]. Furthermore, the mitigation of lung fibrosis has been demonstrated with long-chain ω-3 PUFAs (docosahexaenoic acid (22:6, ω-3)) [ 50 ], short-chain ω-3 PUFA present in flaxseed oil [ 51 , 52 ], and with ω-6 PUFAs, such as γ-linolenic acid (18:3, ω-6) [ 53 ]. The effects attributed to the anti-fibrotic properties of PUFA could be mediated, in part, through their conversion to resolvinD 1 , which inhibits EMT in human alveolar type II cells [ 54 ], and through peroxisome proliferator-activated receptor γ (PPARγ).…”