Cigarette smoke compounds induce cellular redox imbalance, activate NF-κB, and increase TNF-α/CRP secretion: a possible pathway in the pathogenesis of COPD

Abstract

Cigarette smoke has always been considered as a risk factor for chronic obstructive pulmonary diseases (COPD). In this study, we have examined the effect of ten individual cigarette smoke compounds (nicotine, benzo[]pyrene, naphthalene, formaldehyde, ammonia, acrylic acid, toluene, benzene, -xylene, and hexamine) on glutathione transferase (GST) activity, an important Phase II metabolic enzyme and their possible role in inflammatory pathophysiology leading to COPD. Lower Glutathione (GSH) levels and GST activity and higher CRP, TNF-α, and IL-6 levels were observed in COPD patients compared to age and gender-matched controls. Using human recombinant GST and plasma as well as erythrocytes collected from normal subjects this study demonstrates that out of the ten compounds, nicotine (5 mg mL), benzo[]pyrene (10 ng mL), naphthalene (250 μg mL), and formaldehyde (5 pg mL) caused a significant decrease in recombinant, plasma, and erythrocyte GST activity. Further cell culture studies show that exposure to nicotine, benzo[]pyrene, naphthalene, and formaldehyde caused a significant decrease in GSH levels and GST activity and its protein expression and an increase in intracellular ROS production in THP-1 monocytes. Interestingly, treatment with benzo[]pyrene and naphthalene significantly up regulated the phosphorylation of the p65 subunit of NF-κB and increased the secretion of TNF-α and CRP compared to control. This study suggests the potential role of benzo[]pyrene and naphthalene in the activation of the inflammatory signaling pathway leading to cigarette smoke-induced COPD.

Identification of genetic biomarkers, drug targets and agents for respiratory diseases utilising integrated bioinformatics approaches

“…However, in the case of infected lungs, where the genes are differentially expressed, the Benzo[a]pyrene may be used as a therapeutic agent for the treatment of lung diseases, as found in our docked and molecular dynamics study. The potential role of benzo[a]pyrene leads to inducing COPD, and pulmonary inflammation 89 , 90 . Benzo[a]pyrene plays a key role in inducing lung cancer 91 .…”

Antioxidant Potential of Vespa affinis L., a Traditional Edible Insect Species of North East India

“…Fluorescent dye DCFDA (2´,7´-dichlorofluoresceindiacetate) was used to measure the production of intracellular reactive oxygen species (ROS) levels [ 25 ]. The cells were treated AEVA (0.8 μg/μL) or NAC (200 μM) for 2 h followed by H 2 O 2 (25 μM) exposure for the next 2 h. After treatment cells were washed with PBS and then incubated with 5μM DCFDA in PBS containing 4% FBS at 37°C for 30 min in the dark.…”

Chronic Obstructive Pulmonary Disease (COPD)

“…Chronic obstructive pulmonary disease (COPD) may be influenced by race, ethnicity, gender, and genetic factors. Limited data exist that compare COPD in different racial/ethnic groups; however, the available data suggest that differences in COPD may exist [8]. Potential differences in COPD between racial/ ethnic groups include genetic and biological differences; disparities in diagnosis and treatment; increasing exposure to cigarette in nonwhite populations worldwide; and a lack of enrollment of minorities in epidemiological and clinical trials.…”