Jump to main content
Jump to site search

Issue 3, 2016
Previous Article Next Article

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

Author affiliations

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[a]pyrene, naphthalene, formaldehyde, ammonia, acrylic acid, toluene, benzene, m-xylene, and hexamine) on glutathione S 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−1), benzo[a]pyrene (10 ng mL−1), naphthalene (250 μg mL−1), and formaldehyde (5 pg mL−1) caused a significant decrease in recombinant, plasma, and erythrocyte GST activity. Further cell culture studies show that exposure to nicotine, benzo[a]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[a]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[a]pyrene and naphthalene in the activation of the inflammatory signaling pathway leading to cigarette smoke-induced COPD.

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

Back to tab navigation

Publication details

The article was received on 16 Dec 2015, accepted on 01 Mar 2016 and first published on 03 Mar 2016


Article type: Paper
DOI: 10.1039/C5TX00477B
Author version
available:
Download author version (PDF)
Citation: Toxicol. Res., 2016,5, 895-904
  •   Request permissions

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

    T. Dey, P. Dutta, P. Manna, J. Kalita, H. P. D. Boruah, A. K. Buragohain, B. Unni, D. Ozah, M. Kumar Goswami and R. K. Kotokey, Toxicol. Res., 2016, 5, 895
    DOI: 10.1039/C5TX00477B

Search articles by author

Spotlight

Advertisements