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, proinflammatory/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 proinflammatory/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.