Omaveloxolone, CDDO-Me and Obacunone as promising therapeutic options in COPD

Resum

Background: Chronic Obstructive Pulmonary Disease (COPD) is an irreversible progressive inflammatory lung disease. Cigarette smoking is the principal cause in this condition. Inflammation and oxidative stress are important features in the pathogenesis of the disease. Nuclear Factor Erythroid 2-related (Nrf2) is critical in cytoprotection by inducing expression of antioxidant enzymes.Methods: Peripheral blood neutrophils and primary human bronchial cells (HBEC) from COPD and healthy volunteers, as well as, human monocytes were pre-incubated with the drugs and stimulated with cigarette smoke extract (CSE). Gene and protein expression, cytokine release, apoptosis, GSH and ROS levels were measured by RT-PCR, western-blot, ELISA, flow cytometry and luminescent and fluorescent assays, respectively.Aim: To feature Omaveloxolone, Bardoxolone Methyl (CDDO-Me) and Obacunone as antioxidant drugs in COPD.Results: Expression and immunohistochemistry assays using lung tissue and blood from COPD and healthy volunteers showed a negative correlation between the expression of antioxidant genes and proteins and the disease severity. HBEC and neutrophils displayed an increase in antioxidant gene and protein expression, as well as, a decrease in the release of proinflammatory cytokines after stimulation with CSE and drug treatment. In addition, GSH and ROS assays showed that these drugs were able to revert the oxidative stress state in HBEC and inflammatory cells. Moreover, these drugs were highly effective in apoptosis inhibition.Conclusions: Omaveloxolone, CDDO-Me and Obacunone show a huge antioxidant protective effect in CSE-induced COPD by Nrf2 activation. Thus, these drugs may represent a promising therapeutic option in COPDFootnotes Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 180.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at [www.ers-education.org][1] (ERS member access only). [1]: http://www.ers-education.org