Role of cytochrome P450 in the induction of pathological conditions
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Abstract
Cytochrome P450s (CYP450s) are a superfamily of enzymes responsible for metabolism of various chemicals, producing intermediates as reactive oxygen species (ROS) during the process. Accumulation of ROS in cells and tissues alters the balance between oxidants and anti-oxidants in the cells, resulting in oxidative stress which causes pathology in body according to where it occurs. CYP450s are comprised of numerous isoforms. Each isoform play a role in metabolism of different chemicals. Hence, induction of different CYP450 isoforms results in different pathologic diseases. For example, CYP2C induction results in vascular damage via production of leukotoxin and oxynitrate free radicals. Induction of CYP2E leads to hepatic, central nervous system, and cardiac damage, and breast cancer from induction of ROS production. Induction of CYP2D causes damage of central nervous system due to alteration of neurotransmitter metabolisms. Induction of CYP3A results in oxidative stress in liver and hepatotoxicity. Induction of CYP4A damages renal arteries, and then results in renal ischemia. Therefore, consumption of chemicals, including drugs, foods, herbs, or toxicants, which can induce CYP450 enzymes may lead to pathologic conditions via induction of oxidative stress from activation of CYP450s.
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