Pulmonary toxicity and environmental contamination: radicals, electron transfer, and protection by antioxidants.
The atmosphere is replete with a mixture of toxic substances, both natural and man-made. Inhalation of toxic substances produces a variety of insults to the pulmonary system. Lung poisons include industrial materials, particulates from mining and combustion, agricultural chemicals, cigarette smoke, ozone, and nitrogen oxides, among a large number of other chemicals and environmental contaminants. Many proposals have been advanced to explain the mode of action of pulmonary toxicants. In this review we focus on mechanisms of pulmonary toxicity that involve ET, ROS, and OS. The vast majority of toxicants or their metabolites possess chemical ET functionalities that can undergo redox cycling. Such recycling may generate ROS that can injure various cellular constituents in the lung and in other tissues. ET agents include quinones, metal complexes, aromatic nitro compounds, and conjugated iminium ions. Often, these agents are formed metabolically from parent toxicants. Such metabolic reactions are often catalytic and require only small amounts of the offending material. Oxidative attack is commonly associated with lipid peroxidation and oxidation of DNA, and it may result in strand cleavage and 8-OH-DG production. Toxicity is often accompanied by depletion of natural AOs, which further exacerbates the toxic effect. It is not surprising that the use of AOs, both natural in fruits and vegetables, as well as synthetic, may provide protection from the adverse effects of toxicant exposure. The mechanistic framework described earlier is also applicable to some of the more prominent pulmonary illnesses, such as asthma, COPD, and cancer.
Kovacic
Peter
P
Department of Chemistry, San Diego State University, San Diego, CA 92182-1030, USA. pkovacic@sundown.sdsu.edu
Somanathan
Ratnasamy
R
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004579:Electron Transport; D004785:Environmental Pollutants / Q000633:toxicity*; D005609:Free Radicals; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D004785:Environmental Pollutants; D005609:Free Radicals; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species