Superfund Research Program
Chemoprevention of Asbestos-induced Lung Diseases
Dietary flaxseed supplementation was found to provide a chemoprevention strategy for chemically induced lung carcinogenesis by altering signaling pathways, inflammation, and oxidative stress. Using the lignan component in flaxseed consisting mostly of Secoisolariciresinol diglucoside (SDG), the Chemoprevention of Asbestos-Induced Lung Diseases Project, lead by Melpo Christofidou-Solomidou, Ph.D., showed that SDG protects normal cells from radiation damage and prevents asbestos-induce oxidative stress and peritoneal inflammation in mice and radiation-induced damage. Myeloperoxidase (MPO) is a critical enzyme involved in innate immune response and microbial killing. During inflammation and infection, MPO generates hypochlorous acid (HOCl). Christofidou-Solomidou and his researchers revealed that SDG and its synthetic version, LGM2605, inhibits both human and murine MPO activity. Electron paramagnetic resonance (EPR) spectroscopy determined that LGM2605 inhibits MPO by decreasing the formation of highly oxidative Compound I, an intermediate formed in MPO’s catalytic cycle (Mishra OP, Popov AV, Pietrofesa RA, Nakamaru-Ogiso E, Andrake M, Christofidou-Solomidou. M. Biochim Biophys Acta Gen. Sub. 2018). In addition, the researchers also investigated the properties of LGM2605 as a radioprotector and a free radical scavenger and proved that adding LGM2605 30 minutes post radiation exposure significantly decreased the effects caused by space-relevant radiation exposure (Chatterjee S, Pietrofesa RA, Park K, Tao JQ, Carabe-Femandez A, Berman AT, Koumenis C, Sielecki T, Christofidou-Solomidou M. Int J Mol Sci. 2019). LGM2605 was also found to be protective in a murine model of septic cardiopathy, by mediated in part by improvement of mitochondrial function in cardiac myocytes (Kokkinaki D, et. al. J. Mol. Cell. Cardiol., 2019).