Oxidative Stress and Smoke-Related Lung Diseases: A Tentative Approach Through the Blood, Lungs, and Gut

Respiration renders the lungs vulnerable to infectious agents, smoke, and hazardous material that are inhaled in the process. During respiration, oxidants deposit in the lung which can cause oxidative stress and impair the defense mechanism. Due to the subsequent tissue damage, the antioxidant system is not always able to tackle the reactive oxygen species (ROS). When oxidative stress results in tissue damage, progenitor cells try to replace the tissue damaged by the ROS, where the regenerative capacity of the lungs plays a crucial role in preventing further lung damage or disease. Studying molecular pathways of lung cell regeneration is essential in the study of regenerative biology, although regeneration might fail to entirely replace the resulting tissue damage and lead to pathophysiological conditions. The lungs are prone to tissue damage due to continuous exposure to both endogenous and exogenous oxidative mediators and other oxidants, making the process of lung repair extremely important. Some of the damaged tissue can’t be repaired as the repair process cannot match up to the high levels of oxidant exposure resulting in disturbed oxidant and antioxidant balance, thus impacting the normal physiology. Concurrently, ROS and RNS cause oxidative damage and tissue dysfunction in pathological conditions of the lungs. They are responsible for the declining cellular function and compromised mitochondrial system. Prolonged exposure to tobacco and cigarettes is one of the main causative substances in the progression of oxidative stress, a detrimental process that can even lead to lung carcinogenesis. The knowledge in mechanisms of oxidative stress in the lung could lead to improved pharmacological manipulation of antioxidants in lung inflammation as well as injury. Tobacco carcinogens are involved in the upregulation of the redox-sensitive transcription factors and proinflammatory gene expression. Antioxidant defense mechanism consisting of antioxidant enzymes, proteins, and small molecules are impaired in most lung pathologies. Recent clinical investigations aim to develop precise treatment modalities targeting the functioning mechanism of antioxidants against oxidants. This will help in therapeutic management and improved treatment of respiratory diseases.