Antioxidant Treatment To Block Lung Inflammation Caused By Cigarette Smoke

Smoking is a harmful addiction responsible for several lung pathologies caused by toxicity of the cigarette smoke. One of them is chronic obstructive pulmonary disease (COPD), characterized by a chronic cough, respiratory secretions, and progressive dyspnea and fibrosis, produced by chronic exposure of susceptible individuals to cigarette smoke (CS).  In addition to cigarette smoke, other factors such as high exposure to dust, chemicals, and genetic factors could promote COPD.

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Although of a different etiology, COPD and Cystic Fibrosis (CF) share similar respiratory symptoms. CF is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes a chloride channel. In both diseases, a strong inflammatory response and oxidative stress extent constitute indicators of severity of these diseases. The knowledge of the existence of a vicious circle between inflammation and oxidative stress highlight the importance of a therapeutic approach to turning off this damaging circle. Thus, the use of antioxidant drugs for the treatment of these respiratory diseases could enhance the results obtained by traditional treatments applied to patients with these disorders.

In the last years, the antioxidant N-acetylcysteine (NAC) has emerged as a mucolytic, antioxidant, and anti-inflammatory drug for the treatment of respiratory diseases. To test the potential of the antioxidant treatment in COPD, we used a simple model system made with Calu-3 airway cells cultured in vitro exposed to cigarette smoke extract (CSE). The cigarette smoke contains more than 3500 compounds, many of them with toxic activity against the human organism, in many cases by inducing enhanced reactive oxygen species (ROS) production. ROS are highly oxidant molecules and when its production exceeds the antioxidant cellular defense result harmful to cell organelles, proteins, lipids, and other compounds, even reaching the DNA and producing irreversible DNA mutation that eventually produces cancer.

The exposition to CSE caused a reduction in the CFTR expression, an increase in the ROS production and in the expression/secretion of the cytokines IL-6 and IL-8, two proinflammatory markers. Interestingly, the increased secretion of these cytokines was blocked by treatment with the antioxidant NAC, suggesting that the prevention of high levels of ROS could serve as an anti-inflammatory treatment against cigarette smoke injury.

However, a fast induction of mitochondrial ROS (mtROS) and a later mitochondrial Complex I-III activity impairment was also observed, which could not be improved with NAC treatment. Thus, while the NAC effects over ROS and cytokine levels suggest that an antioxidant treatment may help to reduce inflammation in COPD, the results obtained evidence the need for an antioxidant therapy specifically directed to reduce the mitochondrial oxidative stress caused by CSE, which could not be reverted with NAC treatment. In recent years, several drugs have been reported as mitochondrial antioxidants, such as MitoQ10 or SkQ1, that could have beneficial effects on the treatment of respiratory diseases.

These findings are described in the article entitled N-acetyl cysteine reverts the proinflammatory state induced by cigarette smoke extract in lung Calu-3 cells, recently published in the journal Redox BiologyThe work was conducted by Ángel G. Valdivieso, Verónica Sotomayor, Mariángeles Clauzure, Tomás A. Santa-Coloma, in the Laboratory of Cell and Molecular Biology, Institute for Biomedical Research (BIOMED, UCA-CONICET), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA) and The National Scientific and Technical Research Council of Argentina (CONICET), and by Andrea V. Dugour and Juan M. Figueroa from the Fundación Pablo Cassará, Buenos Aires, Argentina.

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Cite this article as:
Tomás A. Santa-Coloma & Angel G. Valdivieso. Antioxidant Treatment To Block Lung Inflammation Caused By Cigarette Smoke, Science Trends, 2018.
DOI: 10.31988/SciTrends.29302
*Note, DOIs are registered Friday weekly and therefore may not work until then.

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