Oxidative Stress Mechanisms in the Pathogenesis of Environmental Lung Diseases

ABSTRACT: Globally, respiratory diseases are major cause of disability and mortality, and more alarmingly, it disproportionately affects developing countries, which is largely attributed to poor quality of air. Tobacco smoke and emissions from combustion of fossil fuel and biomass fuel are the major airborne pollutants affecting human lung health. Oxidative stress is the dominant driving force by which the airborne pollutants exert their toxicity in lungs and cause respiratory diseases. Most airborne pollutants are associated with intrinsic oxidative potential and, additionally, stimulate endogenous production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Elevated ROS and RNS in lungs modulate redox signals and cause irreversible damage to critical biomolecules (lipids, proteins and DNA) and initiate various pathogenic cellular process. This chapter provides an insight into oxidative stress-linked pathogenic cellular process such as lipid peroxidation, inflammation, cell death, mitochondrial dysfunction, endoplasmic reticulum stress, epigenetic changes, profibrotic signals and mucus hypersecretion, which drive the development and progression of lung diseases. Lungs are associated with robust enzymatic and non-enzymatic (GSH, ascorbic acid, uric acid, vitamin E) antioxidant defences. However, sustained production of free radicals due to continuous exposures to airborne pollutants overwhelms lung antioxidant defences and causes oxidative injury. Preclinical studies have demonstrated the critical roles and therapeutic potential of upregulating lung antioxidants for intervention of respiratory diseases; however, so far clinical benefits in antioxidant supplementation trials have been minimal and conflicting. Antioxidants alone may not be effective in treatment of respiratory diseases; however it could be a promising adjunctive therapy.

SUBMITTER: Chakraborti S 

PROVIDER: S-EPMC7120104 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature