| Cytochrome P450 enzymes in the liver catalyze reactions involving the reduction of molecular oxygen and the oxidation of organic substrates. In some cases the resulting products may have the potential to contribute to oxidative stress within this organ. Oxidative stress usually involves the generation of very reactive compounds that can damage cellular components and are therefore harmful to the body. These reactive compounds can include hydrogen peroxide, superoxide, hydroxyl radicals, and a host of other metabolic intermediates (1). Oxidative stress occurs in alcoholics in the liver when an individual consumes harmful amounts of alcohol which can lead to the production of any one or more of the compounds listed above (2).;Cytochrome P450 enzymes have been linked to increased development of oxidative stress in the liver of alcoholics (2). Cytochrome P4502E1 (CYP2E1) can cause mitochondrial stress and disruption via hydrogen peroxide productions which disturbs signaling pathways between cells (3). On the other hand, Cytochrome P4502A6 (CYP2A6) has been shown to activate several known potent carcinogens found in tobacco smoke (4). Cytochrome P4503A4 (CYP 3A4) is a widely recognized enzyme that plays a major role in the metabolism of pharmaceutical drugs, in fact more than 50% of all drugs are metabolized by this enzyme.;This study was designed to attempt to expand the knowledge of Cytochrome P450 inhibition by this series of citrus essential oils by studying their effects on Cytochrome P4502E1, Cytochrome P4503A4 and Cytochrome P4502A6. Here the goal was to determine if any of the nine citrus essential oils would inhibit any of the three Cytochrome P450 enzymes and if so then it would be determined how potent each citrus essential oil is and by what type of inhibition it occurred and determine the correlation between limonene, the main component in each citrus essential oil, and potency of each citrus essential oil. The results for CYP2E1 concluded that Citrus tangerine, tangerine, with a KI value of 4 mug/mL was the most potent inhibitor and Citrus aurantium, neroli, with a KI value of 14 mug/mL was the least potent inhibitor. The results for CYP3A4 concluded that none of the nine citrus essential oils inhibited the activity of CYP3A4 at a good quality concentration. Lastly, the results for CYP2A6 concluded that both Citrus bergamia, bergamot, and Citrus aurantifolia, lime, were the most potent inhibitors with a KI of 0.81 mug/mL and a KI of 1.4 mug/mL. It was concluded that bergamot oil contained 3.46 mM of limonene, grapefruit had 7.84 mM, lemon 4.24 mM, lime 3.75 mM, mandarin 3.79 mM, neroli 4.14 mM, orange 6.65 mM, and tangerine had 5.92 mM of limonene. Petitgrain oil was the only oil that a limonene concentration was unable to be detected, which is expected according to literature reviews which say petitgrain oil only has a 1-2% content of limonene. |
