Cigarette smoke compounds induce cellular redox imbalance, activate NF-κB, and increase TNF-α/CRP secretion: a possible pathway in the pathogenesis of COPD. Issue 3 (14th March 2016)

• Record Type: Journal Article
• Authors: Dey, Tapan; Dutta, Prachurjya; Manna, Prasenjit; Kalita, Jatin; Boruah, Hari Prasanna Deka; Buragohain, Alak Kumar; Unni, Balagopalan; Ozah, Dibyajyoti; Kumar Goswami, Mihir; Kotokey, Ratan Kumar
• Is Part Of: Toxicology research. Volume 5:Issue 3(2016:May)
• Page Start: 895
• Page End: 904
• Publication Date: 2016-03-14
• Subjects: Toxicology -- Periodicals; 615.9005
• DOI: 10.1039/c5tx00477b
• Languages: English
• ISSNs: 2045-452X

Abstract

Graphical Abstract: 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.