Cigarette Smoke Exposure In Lung Research Articles

Cigarette Smoke Induces Distinct Histone Modifications in Lung Cells: Implications for the Pathogenesis of COPD and Lung Cancer

Cigarette smoke (CS)-mediated oxidative stress induces several signaling cascades, including kinases, which results in chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation). We have previously reported that CS induces chromatin remodeling in pro-inflammatory gene promoters; however, the underlying site-specific histone marks formed in histones H3 and H4 during CS exposure in lungs in vivo and in lung cells in vitro, which can either drive gene expression or repression, are not known. We hypothesize that CS exposure in mouse and human bronchial epithelial cells (H292) can cause site-specific posttranslational histone modifications (PTMs) that may play an important role in the pathogenesis of CS-induced chronic lung diseases. We used a bottom-up mass spectrometry approach to identify some potentially novel histone marks, including acetylation, monomethylation, and dimethylation, in specific lysine and arginine residues of histones H3 and H4 in mouse lungs and H292 cells. We found that CS-induced distinct posttranslational histone modification patterns in histone H3 and histone H4 in lung cells, which may be considered as usable biomarkers for CS-induced chronic lung diseases. These identified histone marks (histone H3 and histone H4) may play an important role in the epigenetic state during the pathogenesis of smoking-induced chronic lung diseases, such as chronic obstructive pulmonary disease and lung cancer.

The Field of Tissue Injury in the Lung and Airway

The concept of field cancerization was first introduced over 6 decades ago in the setting of oral cancer. Later, field cancerization involving histologic and molecular changes of neoplasms and adjacent tissue began to be characterized in smokers with or without lung cancer. Investigators also described a diffuse, nonneoplastic field of molecular injury throughout the respiratory tract that is attributable to cigarette smoking and susceptibility to smoking-induced lung disease. The potential molecular origins of field cancerization and the field of injury following cigarette smoke exposure in lung and airway epithelia are critical to understanding their potential impact on clinical diagnostics and therapeutics for smoking-induced lung disease.

Antioxidant effect of diphenyl diselenide on oxidative damage induced by smoke in rats: Involvement of glutathione

In the present study, the involvement of glutathione system in the restorative effect of diphenyl diselenide (PhSe)2 on damage induced by cigarette smoke was investigated. Rat pups were progressively exposed to four, five, and six cigarettes for exposure periods of 15min during their first, second, and third weeks of life. Thiobarbituric acid reactive species (TBARS) levels, components of the enzymatic antioxidant defenses (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities), and non-enzymatic antioxidant defenses (vitamin C and non-protein thiol (NPSH) levels) were examined in lungs of pups. The results demonstrated an increase in lipid peroxidation and the alteration in non-enzymatic and enzymatic antioxidant defenses induced by cigarette smoke exposure in lung of pups. Administration of (PhSe)2 (0.5mg/kg) restored TBARS levels and antioxidant defenses in lungs of rat pups exposed to cigarette smoke. (PhSe)2 treatment increased NPSH levels and GST activity per se in lungs of rat pups. Together these results indicate that (PhSe)2 restored oxidative damage induced by cigarette smoke exposure in lungs of rat pups. The glutathione system is involved in antioxidant effect of this compound.

Diphenyl diselenide prevents oxidative damage induced by cigarette smoke exposure in lung of rat pups

The effect of cigarette smoke exposure on lungs of rat pups was evaluated. Animals were exposed to passive cigarette smoke during 3 weeks and a number of toxicological parameters in lung of pups were examined, such as lipid peroxidation, δ-aminolevulic acid dehydratase (δ-ALA-D) activity, components of the enzymatic antioxidant defenses (superoxide dismutase (SOD) and catalase activities) and non-enzymatic antioxidant defenses (Vitamin C and non-protein thiol (NPSH) levels). Furthermore, a possible protective effect of diphenyl diselenide, (PhSe) 2, was studied. The results demonstrated an increase in lipid peroxidation, an inhibition of δ-ALA-D activity, a reduction of Vitamin C and NPSH levels induced by cigarette smoke exposure, indicating damage in lungs of rat pups. Oral administration of (PhSe) 2 (0.5 mg/kg) restored TBARS levels, non-enzymatic antioxidant defenses and activity of δ-ALA-D. These results indicated that exposure to cigarette smoke enhanced oxidative stress, thereby disturbing the tissue defense system. (PhSe) 2 protected against oxidative damage induced by cigarette smoke exposure in lung of rat pups.