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Molecular Therapeutic Targets in Tobacco-Induced Lung Pathology

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Oxidative Stress in Lung Diseases

Abstract

Tobacco consumption globally is estimated to be around 20% and in India accounted for 12% of the world’s smokers according to the World Health Organization (WHO) statistics. It is also estimated that around six million deaths occur every year and rises to eight million by the year 2030. The socioeconomic health burden is of great concern due to the rise in cigarette smoking and related deaths. Cigarette smoking is known to cause many disorders such as chronic obstructive pulmonary diseases (COPD), oral cancers, and pulmonary tumors. More than 6000 different chemicals contain approximately 100 known pulmonary carcinogens present in the cigarette smoke (CS). Inhaled polycyclic aromatic hydrocarbons (PAHs), constituents of CS, are deposited in the airway epithelium and the majority in the alveolar epithelium which detoxifies the cigarette constituents by way of drug-metabolizing enzymes such as cytochrome p450 (CYP450) enzymes. Reactive oxygen species (ROS) present in the CS and the CS-mediated generation of mitochondrial and cellular ROS have an impact on the cellular bio-constituents such as membrane lipids, proteins, and DNA. Studies suggest that oxidative stress causes lung inflammation by remodeling of membrane lipids and pulmonary surfactants via activation of phospholipase A2 (PLA2), cyclooxygenases (COX), and lipoxygenases which directly or indirectly activates proinflammatory cytokines. Considering the complexity of lung tissue and functions, understanding the cellular and tissue mechanisms of damage and strategies overcoming the deleterious effects mediated by the CS would be prime importance. This understanding helps target specific molecules that will help in developing therapeutic strategies to circumvent the CS-mediated disease burden, mortality, morbidity, and economic burden.

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Avti, P.K., Khanduja, K.L. (2019). Molecular Therapeutic Targets in Tobacco-Induced Lung Pathology. In: Chakraborti, S., Chakraborti, T., Das, S., Chattopadhyay, D. (eds) Oxidative Stress in Lung Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-13-8413-4_23

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