Cytochrome P450 and Health Hazards of Smog

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The rising levels of smog, blanketing northern parts of India during October-January in recent years, have pushed pollution levels to an extremely hazardous point. The pollutants and the particulate matter (PM) generated by various activities have a very harmful effect on human health. This has resulted in an increase in human diseases, especially of the respiratory and cardiovascular organ systems. Combustion results in the formation of redox-active metals and aromatic hydrocarbons, which stay in the environment long after the activity has ceased. These moieties form air-stable, environmentally persistent free radicals on entrained particles that harm the pulmonary and cardiovascular systems. The protective mechanisms of the bronchopulmonary tract are unable to stop the ultra-fine air pollutants from invading the body. The various by-products of smog enter the human body via several different routes, finally reaching the liver for detoxification by Cytochrome P450 (also known as CYPs). Negative health effects of air pollutants have been shown on the cardiovascular system resulting in multiple respiratory diseases, including respiratory infections, asthma, chronic obstructive pulmonary disease (COPD), lung cancer, even in combination with stroke and heart diseases. The CYPs are endoplasmic reticulum resident enzyme systems that are involved in the metabolism of xenobiotics as well as drugs. The free radicals have a deleterious effect on these enzymes and have been found to inhibit six forms of P450 in rat liver microsomes. These free radicals are thought to inhibit CYP2B4-mediated substrate metabolism by physically disrupting the CPR•P450 complex.