Assessing the Free Radical Scavenging Ability and Antioxidant Efficiency of a Synthetic Flaxseed Lignan in an Asbestos Exposure Model
Additional Funding Sources
The project described was supported by the Idaho State University Biology department (internal funding).
Abstract
Asbestos exposure is known to cause pleural fibrosis, asbestosis, and other respiratory conditions, as well as systemic autoimmune disease (SAID). In order to help treat/prevent such illnesses, we are investigating the therapeutic potential of LGM2605, a synthetic derivative of the flaxseed lignan secoisolariciresinol diglucoside (SDG). This drug is an antioxidant and free radical scavenger which may block early immune responses (i.e. inflammation) observed with asbestos exposure. Studies have shown that mesothelial cells act as key regulators of inflammation through activation of the NLRP-3 inflammasome and the production of pro-inflammatory cytokines. Thus, we predicted that LGM2605 may help reduce these activities. We performed several DCFDA ROS assays comparing the production of reactive oxygen species (ROS) in mesothelial cells exposed to various asbestos fiber types. We found that Libby Amphibole (LA) fibers yield the highest level of ROS activity, suggesting higher levels of inflammasome activation and pathogenicity. Next, we performed additional ROS assays to determine the effects of LGM2605 treatment. We found that LGM2605 reduces ROS production in mesothelial cells exposed to asbestos fibers, which we suspect may also reduce inflammasome activation. Subsequent investigation will determine the effects of LGM2605 treatment in mice that have been exposed to LA through intraperitoneal injection.
Assessing the Free Radical Scavenging Ability and Antioxidant Efficiency of a Synthetic Flaxseed Lignan in an Asbestos Exposure Model
Asbestos exposure is known to cause pleural fibrosis, asbestosis, and other respiratory conditions, as well as systemic autoimmune disease (SAID). In order to help treat/prevent such illnesses, we are investigating the therapeutic potential of LGM2605, a synthetic derivative of the flaxseed lignan secoisolariciresinol diglucoside (SDG). This drug is an antioxidant and free radical scavenger which may block early immune responses (i.e. inflammation) observed with asbestos exposure. Studies have shown that mesothelial cells act as key regulators of inflammation through activation of the NLRP-3 inflammasome and the production of pro-inflammatory cytokines. Thus, we predicted that LGM2605 may help reduce these activities. We performed several DCFDA ROS assays comparing the production of reactive oxygen species (ROS) in mesothelial cells exposed to various asbestos fiber types. We found that Libby Amphibole (LA) fibers yield the highest level of ROS activity, suggesting higher levels of inflammasome activation and pathogenicity. Next, we performed additional ROS assays to determine the effects of LGM2605 treatment. We found that LGM2605 reduces ROS production in mesothelial cells exposed to asbestos fibers, which we suspect may also reduce inflammasome activation. Subsequent investigation will determine the effects of LGM2605 treatment in mice that have been exposed to LA through intraperitoneal injection.
Comments
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