High Levels of Dioxin-Like Potential in Cigarette Smoke Evidenced by In vitro and In vivo Biosensing

The proteinase-antiproteinase theory for the pathogenesis of emphysema proposes that the connective tissue destruction associated with emphysema arises from excessive proteinase activity in the lower respiratory tract. For this reason, the relative activities of neutrophil elastase and alpha 1-proteinase inhibitor (alpha 1-PI) are considered important. Most emphysema is observed in smokers; therefore, alpha 1-PI has been studied as a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could occur by several mechanisms involving species delivered to the lung by cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to alpha 1-PI has received particular attention, since both cigarette smoke and inflammatory cells are rich sources of oxidants. In this article we review almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 1-PI at the molecular and functional levels.

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Cigarette smoke and phagocyte function: effect of chronic exposure in vivo and acute exposure in vitro.

Infection and Immunity ◽

10.1128/iai.20.2.468-475.1978 ◽

1978 ◽

Vol 20 (2) ◽

pp. 468-475 ◽

Cited By ~ 23

Author(s):

W R Thomas ◽

P G Holt ◽

D Keast

Keyword(s):

Cigarette Smoke ◽

Chronic Exposure ◽

Acute Exposure ◽

Exposure In Vivo

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INACTIVATION OF ALPHA1-PROTEINASE INHIBITOR AND BRONCHIAL MUCOUS PROTEINASE INHIBITOR BY CIGARETTE SMOKE IN VITRO AND IN VIVO

Biochemistry, Pathology and Genetics of Pulmonary Emphysema ◽

10.1016/b978-0-08-027379-2.50034-x ◽

1981 ◽

pp. 321-340

Author(s):

A. Janoff ◽

H. Carp ◽

D.K. Lee

Keyword(s):

Cigarette Smoke ◽

Proteinase Inhibitor

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Oral cancer, cigarette smoke and mitochondrial 18kDa translocator protein (TSPO) — In vitro, in vivo, salivary analysis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2010.01.008 ◽

2010 ◽

Vol 1802 (5) ◽

pp. 454-461 ◽

Cited By ~ 19

Author(s):

Rafael Nagler ◽

Ofer Ben-Izhak ◽

Dana Savulescu ◽

Ella Krayzler ◽

Sharon Akrish ◽

...

Keyword(s):

Oral Cancer ◽

Cigarette Smoke ◽

Translocator Protein

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Humic-like substances in cigarette smoke condensate and lung tissue of smokers

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1994.266.4.l382 ◽

1994 ◽

Vol 266 (4) ◽

pp. L382-L388 ◽

Cited By ~ 6

Author(s):

A. J. Ghio ◽

J. Stonehuerner ◽

D. R. Quigley

Keyword(s):

Free Radical ◽

Cigarette Smoke ◽

Lung Tissue ◽

Cigarette Smoke Exposure ◽

Cigarette Smoke Condensate ◽

Free Radical Generation ◽

Carboxylate Content ◽

Radical Generation

Deposition of pigmented matter in the lower respiratory tract correlates with the extent of emphysema in smokers as well as with free radical generation and iron accumulation. Pulmonary emphysema is postulated to be mediated by free radical generation which is either directly or indirectly associated with cigarette smoke exposure. The hypothesis was tested that 1) incomplete combustion of tobacco yields humic-like substances (HLS) which 2) deposit in the lung as pigmented particulates, 3) complex iron cations in vitro and in vivo, and 4) have a capacity to catalyze oxidant formation. HLS, isolated by alkali extraction of cigarette smoke condensate (CSC) (Tobacco Health Research Institute, University of Kentucky), demonstrated a high carbon and low carboxylate content on elemental and functional group analyses, respectively, compared with values for HLS sequestered from soils. The HLS isolated from CSC had a capacity to complex iron in vitro and accumulated the metal in vivo after intratracheal instillation in an animal model. Both HLS and its iron complex generated free radicals, and some portion of this oxidant generation was metal dependent. Lung tissue collected at autopsy from smokers contained HLS with an infrared spectrum almost identical to that of the material isolated from CSC. Associations between particulate deposition, metal accumulation, and free radical generation suggest a possible role of HLS in the induction of lung disease following cigarette exposure.

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Ergosterol attenuates cigarette smoke extract-induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo

Clinical Science ◽

10.1042/cs20190331 ◽

2019 ◽

Vol 133 (13) ◽

pp. 1523-1536 ◽

Cited By ~ 8

Author(s):

Xiao Sun ◽

Xiuli Feng ◽

Dandan Zheng ◽

Ang Li ◽

Chunyan Li ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Cigarette Smoke Extract ◽

Cordyceps Sinensis ◽

Chronic Obstructive ◽

Therapeutic Effects ◽

Related Proteins ◽

And Oxidative Stress

Abstract Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). CS heightens inflammation, oxidative stress and apoptosis. Ergosterol is the main bioactive ingredient in Cordyceps sinensis (C. sinensis), a traditional medicinal herb for various diseases. The objective of this work was to investigate the effects of ergosterol on anti-inflammatory and antioxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both in vitro and in vivo. Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the nuclear factor kappa B (NF-κB)/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), malondialdehyde (MAD) and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-poly-(ADP)-ribose polymerase (PARP) both in vitro and in vivo, whereas decreased the levels of superoxide dismutase (SOD) and catalase (CAT). Treatment of 16HBE cells and Balb/c mice with ergosterol inhibited CSE-induced inflammatory and oxidative stress and apoptosis by inhibiting the activation of NF-κB/p65. Ergosterol suppressed apoptosis by inhibiting the expression of the apoptosis-related proteins both in vitro and in vivo. Moreover, the usage of QNZ (an inhibitor of NF-κB) also partly demonstrated that NF-κB/p65 pathway was involved in the ergosterol protective progress. These results show that ergosterol suppressed COPD inflammatory and oxidative stress and apoptosis through the NF-κB/p65 pathway, suggesting that ergosterol may be partially responsible for the therapeutic effects of cultured C. sinensis on COPD patients.

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