The role of NRF2/KEAP1 pathway in the pathogenesis of smoking-related oxidative stress of COPD

Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by airflow limitation and increased chronic inflammatory response. Many genetic and environmental risk factors, especially smoking, play a role in the pathogenesis of the disease. The aim of our study is to investigate the role of the Nrf2/Keap1 pathway in the pathogenesis of smoking-related oxidative stress in COPD, to better understand the underlying pathophysiology, and to determine whether new supportive markers (Nrf2, Keap1, Gsk-3β, malondialdehyde, peroxynitrite) can be used in smoking-related COPD. Thirty one COPD patients who admitted to our clinic, 31 smokers who were not diagnosed with COPD, and 34 non-smokers were included in our study. Routine blood tests of COPD patients were taken. Pulmonary function tests were performed on COPD patients and smokers. Nrf2, Keap-1, Gsk-3β, peroxynitrite and malondialdehyde were studied in peripheral venous blood samples of all three groups. SPSS 22.0 Windows version package program was used in the analysis. In the comparison between COPD patients, smokers, and non-smoker volunteers participating in the study; Nrf2 level was found to be significantly lower in the smoker control group compared to the other two groups. Keap1 level was significantly lower in the COPD group than in both control groups. GSK-3β level was higher in the COPD group (p=0,012). When COPD patients were evaluated in terms of the treatments they received, peroxynitrite was found to be statistically significantly lower in patients using LABA. Peroxynitrite levels were significantly higher in the COPD group. Our data show that there is no significant relationship between Nrf2, Keap1, Gsk-3β, MDA levels and COPD and smoking. Larger studies are needed to elucidate the smoking-related oxidative stress pathogenesis of COPD.