title: Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice.
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, 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.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Pietrofesa
authors.forename: Anastasia
authors.initials: A
authors.lastname: Velalopoulou
authors.forename: Evguenia
authors.initials: E
authors.lastname: Arguiri
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA and.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Menges
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA and.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hwang
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
authors.forename: Melpo
authors.initials: M
authors.lastname: Christofidou-Solomidou
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D002072:Butylene Glycols / Q000008:administration & dosage*; D002853:Chromatography, Liquid; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D019597:Flax; D005960:Glucosides / Q000008:administration & dosage*; D007249:Inflammation / Q000473:pathology*; D017705:Lignans / Q000008:administration & dosage*; D008654:Mesothelioma / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000187:drug effects; D010533:Peritoneal Lavage; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology*; D011230:Precancerous Conditions / Q000188:drug therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012639:Seeds; D053719:Tandem Mass Spectrometry; D059467:Transcriptome
chemical_list: D000975:Antioxidants; D002072:Butylene Glycols; D005960:Glucosides; D017705:Lignans; D017638:Asbestos, Crocidolite; C090142:secoisolariciresinol diglucoside