A Study of Cytochrome P450's Level and Method of Response to the Common Environmental Compound Ethylbenzene
Meisel, Karl M.
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Cytochrome P450 is a super family of enzymes that metabolize a wide variety of endogenous and exogenous compounds. These enzymes are involved in the bioactivation of xenobiotics and drug metabolism, which may cause P450 to either increase or decrease its own enzyme levels as well as the substrate's. In the current study, three specific cytochrome enzymes levels were investigated 2B1, 3A2 and 2C 11. Previous studies demonstrated the responses of these enzymes to a barbiturate, phenobarbital (PB). However, a direct evaluation of the responses of PB to ethylbenzene (EB), an aromatic hydrocarbon found in the environment, will help to yield a better understanding of how the environment may influence P450 drug metabolizing enzymes. Hormones are also known to regulate the expression of various P450 isozymes, therefore this study removed the pituitary gland in order to consider this endogenous factor. The evaluation of P450 2B 1 showed no significant difference in enzyme levels when treated by either PB or EB over a twenty-four hour period. The removal of the pituitary gland, hypophysectomy, demonstrated that PB increases 2B 1 levels even in the absence of endogenous hormones. Ethylbenzene (EB), however, does not increase the enzyme levels in the absence of pituitary gland. Therefore indicating that the similar induction levels of 2B1 caused by PB and EB may occur through two different mechanisms. In the evaluation of P450 3A2 no significant difference existed between the enzyme levels of the EB and PB responses in both intact and hypophysectomized (hypox) rats. This indicates that similar mechanisms may be involved in the enzyme's response to both EB and PB. Cytochrome P450 2C11 also demonstrated no overall significant difference between EB and PB induced responses in both intact and hypox rats. Therefore, a similar mechanism may be involved in the mediation of 2CII by both the drug PB and the environmental factor EB.