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

Pietrofesa, Ralph A.; Velalopoulou, Anastasia; Arguiri, Evguenia; Menges, Craig W.; Testa, Joseph R.; Hwang, Wei–Ting; Albelda, Steven Μ.; Christofidou‐Solomidou, Melpo

doi:10.1093/carcin/bgv174

Cited by 45 publications

(60 citation statements)

References 57 publications

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“…The mechanism of the LGM2605 action in protecting against oxidative damage is thought to involve both free radical scavenging and induction of antioxidant enzymes. [18][19][20][21][22]27,28 To investigate the effects of LGM2605, we used a different model of radiation lung injury (described in the Methods section in this article's Online Repository).…”

Section: Results O 3 -Induced Increases In Ahr Were Prevented By Antimentioning

confidence: 99%

Ozone-induced enhancement of airway hyperreactivity in rhesus macaques: Effects of antioxidant treatment

Flayer

Larson

Joseph

et al. 2020

Journal of Allergy and Clinical Immunology

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Background: Ozone (O 3) inhalation elicits airway inflammation and impairs treatment responsiveness in asthmatic patients. The underlying immune mechanisms have been difficult to study because of the lack of relevant experimental models. Rhesus macaques spontaneously have asthma and have a similar immune system to human subjects. Objectives: We sought to investigate mucosal immune changes after O 3 inhalation in a clinically relevant nonhuman primate asthma model and to study the effects of an antioxidant synthetic lignan (synthetic secoisolariciresinol diglucoside [LGM2605]). Methods: A cohort of macaques (n 5 17) previously characterized with airway hyperreactivity (AHR) to methacholine was assessed (day 1). Macaques were treated (orally) with LGM2605 (25 mg/kg) or placebo twice per day for 7 days, exposed to 0.3 ppm O 3 or air for 6 hours (on day 7), and studied 12 hours later (day 8). Lung function, blood and bronchoalveolar lavage (BAL) fluid immune cell profile, and bronchial brushing and blood cell mRNA expression were assessed. Results: O 3 induced significant BAL fluid neutrophilia and eosinophilia and increased AHR and expression of IL6 and IL25 mRNA in the airway epithelium together with increased BAL fluid group 2 innate lymphoid cell (ILC2s), CD1c 1 myeloid dendritic cell, and CD4 1 T-cell counts and diminished surfactant protein D expression. Although LGM2605 attenuated some of the immune and inflammatory changes, it completely abolished O 3-induced AHR.

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Section: Results O 3 -Induced Increases In Ahr Were Prevented By Antimentioning

confidence: 99%

Ozone-induced enhancement of airway hyperreactivity in rhesus macaques: Effects of antioxidant treatment

Flayer

Larson

Joseph

et al. 2020

Journal of Allergy and Clinical Immunology

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“…We have previously evaluated the ability of a flaxseed lignan diet, enriched in the natural form of biphenolic SDG, to prevent acute asbestos-induced inflammation and oxidative/nitrosative stress in a murine model of peritoneal asbestos exposure [ 24 ]. Specifically, mice fed an FLC diet, enriched in SDG, displayed a 74.6% reduction in levels of the MDA in the peritoneal lavage fluid (PLF) at three days post intraperitoneal asbestos exposure.…”

Section: Discussionmentioning

confidence: 99%

“…In our first study, we evaluated the usefulness of an FLC-supplemented diet in a murine model of acute asbestos-induced peritoneal inflammation and oxidative tissue damage. Three days after intraperitoneal instillation of asbestos into mice, we observed an increase in oxidative and nitrosative stress in the peritoneal fluid, which was significantly attenuated by FLC diet [ 24 ]. These findings have led us to conduct more controlled in vitro studies where we can confirm that the effects were due specifically to the purified compound SDG, show that peritoneal macrophages were a key target in this antioxidant effect, and conduct additional mechanistic studies.…”

Section: Introductionmentioning

confidence: 99%

Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605)

Pietrofesa

Velalopoulou

Albelda

et al. 2016

IJMS

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Abstract:The interaction of asbestos fibers with macrophages generates harmful reactive oxygen species (ROS) and subsequent oxidative cell damage that are key processes linked to malignancy. Secoisolariciresinol diglucoside (SDG) is a non-toxic, flaxseed-derived pluripotent compound that has antioxidant properties and may thus function as a chemopreventive agent for asbestos-induced mesothelioma. We thus evaluated synthetic SDG (LGM2605) in asbestos-exposed, elicited murine peritoneal macrophages as an in vitro model of tissue phagocytic response to the presence of asbestos in the pleural space. Murine peritoneal macrophages (MFs) were exposed to crocidolite asbestos fibers (20 µg/cm 2 ) and evaluated at various times post exposure for cytotoxicity, ROS generation, malondialdehyde (MDA), and levels of 8-iso Prostaglandin F2α (8-isoP). We then evaluated the ability of LGM2605 to mitigate asbestos-induced oxidative stress by administering LGM2605 (50 µM) 4-h prior to asbestos exposure. We observed a significant (p < 0.0001), time-dependent increase in asbestos-induced cytotoxicity, ROS generation, and the release of MDA and 8-iso Prostaglandin F2α, markers of lipid peroxidation, which increased linearly over time.LGM2605 treatment significantly (p < 0.0001) reduced asbestos-induced cytotoxicity and ROS generation, while decreasing levels of MDA and 8-isoP by 71%-88% and 41%-73%, respectively. Importantly, exposure to asbestos fibers induced cell protective defenses, such as cellular Nrf2 activation and the expression of phase II antioxidant enzymes, HO-1 and Nqo1 that were further enhanced by LGM2605 treatment.LGM2605 boosted antioxidant defenses, as well as reduced asbestos-induced ROS generation and markers of oxidative stress in murine peritoneal macrophages, supporting its possible use as a chemoprevention agent in the development of asbestos-induced malignant mesothelioma.

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“…2, 10–13 High intake of dietary sources of lignans, as well as plasma END and ENL concentrations, have been associated with reduced risk of colorectal, 14, 15 prostate, and breast cancer. 16–18 …”

Section: Introductionmentioning

confidence: 99%

Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets

et al. 2017

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Enterolignans, products of gut bacterial metabolism of plant lignans, have been associated with reduced risk of chronic diseases, but their association with other plasma metabolites is unknown. We examined plasma metabolite profiles according to urinary enterolignan excretion in a cross-sectional analysis using data from a randomized crossover, controlled feeding study. Eighty healthy adult males and females completed two 28-day feeding periods differing by glycemic load, refined carbohydrate, and fiber content. Lignan intake was calculated from food records using a polyphenol database. Targeted metabolomics was performed by LC-MS on plasma from fasting blood samples collected at the end of each feeding period. Enterolactone (ENL) and enterodiol (END), were measured in 24-h urine samples collected on the penultimate day of each study period using GC-MS. Linear mixed models were used to test the association between enterolignan excretion and metabolite abundances. Pathway analyses were conducted using the Global Test. Benjamini-Hochberg false discovery rate (FDR) was used to control for multiple testing. Of the metabolites assayed, 121 were detected in all samples. ENL excretion was associated positively with plasma hippuric acid and melatonin, and inversely with epinephrine, creatine, glycochenodeoxycholate, and glyceraldehyde (P <0.05). Hippuric acid only satisfied the FDR of q < 0.1. END excretion was associated with myristic acid and glycine (q <0.5). Two of 57 pathways tested were associated significantly with ENL, ubiquinone and terpenoid-quinone biosynthesis, and inositol phosphate metabolism. These results suggest a potential role for ENL or ENL-metabolizing gut bacteria in regulating plasma metabolites.

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

Cited by 45 publications

References 57 publications

Ozone-induced enhancement of airway hyperreactivity in rhesus macaques: Effects of antioxidant treatment

Ozone-induced enhancement of airway hyperreactivity in rhesus macaques: Effects of antioxidant treatment

Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605)

Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets

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