Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice.

Key Findings:

Pleural malignant mesothelioma (MM) is can develop when inhaled asbestos fibers affect the lung and the pleural surface. Peritoneal MM is caused when inhaled asbestos fibers reach the peritoneum through the lymphatic system. The lignan SDG has been found to modulate growth factor-mediated cell signaling, cell cycle gene expression and apoptosis. This study showed that flax lignan can reduce acute asbestos-induced peritoneal inflammation in a mouse model with genetic alterations in the NF2 genes (Nf2+/mu) which causes accelerated MM development. FS lignans reduced acute inflammation caused by asbestos induced by the IP administration of asbestos. These studies support further research to test the ability of FS lignan to prevent the formation of MM after asbestos exposure.

ABSTRACT:

Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2+/mu mice. Mice (n = 16–17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 μg of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, pro inflammatory profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammator profibrogenic cytokines (IL-1ß, IL- 6, TNFα, HMGB1 and active TGFß1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice.  Importantly, PLF WBC gene expression of cytokines (IL-1ß, IL-6, TNFα, HMGB1 and TGFß1) and cytokine receptors (TNFαR1 and TGFßR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM. (Authors abstract)