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

Our plain-English summary of Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice, by R.A. Pietrofesa, A. Velalopoulou, E. Arguiri, et al (Carcinogenesis, 2016).

The study

• Authors: R.A. Pietrofesa, A. Velalopoulou, E. Arguiri, C.W. Menges, J.R. Testa, W.T. Hwang, S.M. Albelda, M. Christofidou-Solomidou
• Journal: Carcinogenesis
• Published: 2016;37(2):177-87
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© The Author 2015. Published by Oxford University Press.

In plain English

This was an animal experiment in genetically altered (Nf2+/mut) mice, which develop mesothelioma faster after asbestos exposure. Male mice, 13 weeks old, were fed either a control diet (16 mice) or a diet supplemented with flaxseed lignans rich in a compound called SDG (17 mice). The diets started 7 days before a single injection of 400 µg of crocidolite asbestos into the abdomen. Eight uninjected mice provided baseline values. Three days after the injection, the researchers rinsed out the abdominal cavity and measured white blood cells, inflammatory signalling proteins, and markers of oxidative and nitrosative stress. Asbestos raised these measures in control-fed mice. Lignan-fed mice had 58.3% fewer white blood cells than control-fed mice (890 588 versus 2 134 000 cells/ml). They also had lower levels of each inflammatory protein and stress marker measured. The study looked only at short-term inflammation, not at whether tumors formed. The authors concluded that the diet blunted the acute inflammation caused by asbestos and that this supports further research on preventing mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: genetically altered mice fed a control diet or a flaxseed lignan-supplemented diet, then given a single abdominal (intraperitoneal) injection of asbestos and examined 3 days later
• Who was studied: Male Nf2+/mut mice, 13 weeks old in the main experiment: 16 on control diet and 17 on flaxseed lignan diet, plus a group of 8 mice not injected with asbestos that provided baseline values. Earlier preliminary experiments used 7-week-old mice.
• Exposure: A single intraperitoneal injection of 400 µg of UICC crocidolite asbestos fibers. The test treatment was a diet containing 3.37 g/kg flaxseed lignans (1.18 g SDG/kg diet), started 7 days before the asbestos injection.
• Main results:
  • Mice on the lignan diet had 58.3% fewer total white blood cells in abdominal fluid than control-fed mice (890 588 ± 76 957 cells/ml versus 2 134 000 ± 220 076 cells/ml; P < 0.0001).
  • Neutrophil and macrophage concentrations in abdominal fluid were 66.5% and 49.0% lower, respectively, in lignan-fed mice than in control-fed mice (P < 0.001).
  • IL-1ß in abdominal fluid was 2.73 pg/ml at baseline and 15.22 pg/ml in asbestos-exposed control-fed mice, compared with 1.41 pg/ml in asbestos-exposed lignan-fed mice (P < 0.0001).
  • IL-6 was 52.80 pg/ml in asbestos-exposed control-fed mice and 3.47 pg/ml in asbestos-exposed lignan-fed mice (P < 0.0001); the baseline was 0.31 pg/ml.
  • HMGB1 was 57.33 ng/ml in asbestos-exposed control-fed mice (baseline 7.89 ng/ml) and 17.01 ng/ml in lignan-fed mice (P < 0.0001).
  • TNFα was 7.68 pg/ml in asbestos-exposed control-fed mice (baseline 1.43 pg/ml) and 2.35 pg/ml in lignan-fed mice (P < 0.0001).
  • Active TGFß1 was 25.94 pg/ml in asbestos-exposed control-fed mice (baseline 2.20 pg/ml) and 4.52 pg/ml in lignan-fed mice (P < 0.0001).
  • In white blood cells from lignan-fed mice, gene activity (mRNA) for inflammatory proteins was lower than in control-fed mice. For example, IL-1ß mRNA was 61.4% lower.
  • Nitrite, a marker of nitrosative stress, was 1.09 µM in asbestos-exposed control-fed mice (baseline 0.15 µM) and 0.19 µM in lignan-fed mice.
  • MDA, a marker of oxidative stress, was 11.26 nM in asbestos-exposed control-fed mice (baseline 2.08 nM). It was 2.87 nM in lignan-fed mice, a 74.6% reduction.
  • Compared with control-fed mice, lignan-fed mice had 2.31-, 2.00- and 2.30-fold higher white-blood-cell mRNA levels of the protective enzymes HO-1, Nqo1 and Gstm1.
  • In ordinary (wild-type) mice, for which the number of animals is not given, white blood cells after asbestos were also lower on the lignan diet: 368 000 versus 5 140 000 cells/ml (P < 0.01).
• The authors' conclusion: The authors concluded that a diet enriched in the flaxseed lignan SDG blunted the acute inflammatory response caused by injecting asbestos into the abdomen. They said this supports further research into whether the lignan can prevent mesothelioma after asbestos exposure.
• Limitations the authors state:
  • The study examined only acute inflammation over 3 days. Whether the diet prevents tumors after chronic asbestos exposure was not tested and is left to future studies.
  • Humans are usually exposed by breathing in asbestos, whereas these mice received the fibers by injection into the abdomen.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Inflammation, Malignant Mesothelioma, Asbestos Exposure, Latency, Chronic Inflammation, Crocidolite, Cytokine, High Mobility Group Box 1 (HMGB1).

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