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.

Bleomycin, a widely used antineoplastic agent has been associated with severe pulmonary toxicity through production of acute interstitial pneumonia, pulmonary vasculitis and, eventually pulmonary fibrosis. Treatment by omega‐3 fatty acid in flax seed oil may reduce bleomycin induced lung injury. To test this hypothesis 72 rats were equally divided between diets receiving 15% fat as flax seed oil or corn oil (control). These two groups were further divided to receive either 8 units/kg body weight bleomycin or vehicle, intratracheally. Lungs were harvested at 2, 7, or 21 days and tissue was fixed and stained (H&E) for histopathology. Two investigators evaluated the bleomycin induced lung responses particularly the bleomycin‐induced pulmonary vasculitis by photographing five small caliber pulmonary arteries. These arteries were measured for pulmonary lumen patency and the ratio of media diameter/adventitia diameter. At days 7 and 21, bleomycin produced a significant reduction in lumen patency (p=0.01) and of media/adventitial diameter (p=0.02 all days) which was not evident when the rats were treated with the flax seed oil diet. At day 7 the flax seed oil group also showed a delay in edema formation, inflammatory cell infiltrate and reduced pulmonary septal thickness. This model presents a dietary regime which may protect against bleomycin pulmonary toxicity.Support: Wheaton College General Endowment fund.

In earlier work we showed a reduction in bleomycin‐induced pathology by a diet high in flax seed oil. To investigate the protective mechanisms, 36 rats were fed a diet with 15% flaxseed oil 4 wk, and 36 controls received 15% corn oil. These received either 8 units/kg intratracheal bleomycin or vehicle, and lungs were harvested at 2, 7 and 21 days. Tissue was fixed and stained (H&E) for histopathology. Two investigators evaluated inflammatory cell infiltrate, septal thickness, emphysema, medial vasculitis, adventitial vasculitis and edema. Animals receiving flaxseed oil showed a delay in edema formation (p=0.025), and a significant decrease in inflammatory cell infiltrate and vasculitis (p=0.04 and 0.007 respectively) compared to corn oil controls. Rats receiving bleomycin and flaxseed oil had significantly reduced pulmonary septal thickness (p=0.013) over positive controls. No differences were observed among groups at 21 days. The time course for injury (highest at 7 and even 2 days) suggests protection for Clara cells. The significant reduction in septal thickness in the flaxseed oil‐treated groups further suggests protection against fibrotic effects of bleomycin. This model presents a dietary regimen that may prove beneficial against the side effects of this highly effective chemotherapeutic agent and its known toxic effects on the lung. Supported by Wheaton College General Endowment Fund