Cytochrome P450-catalysed arene-epoxidation of the bioactive tea tree oil ingredient p-cymene: indication for the formation of a reactive allergenic intermediate?
ABSTRACT 1. The cytochrome P450-mediated metabolism of the tea tree oil ingredient p-cymene (p-isopropyltoluene) was studied by the application of in vitro enzymatic assays using different recombinant human cytochrome P450 enzymes. 2. In total, four enzymatic products were identified by gas chromatography-mass spectrometry. The enzymatic products identified were: thymol (2-isopropyl-5-methylphenol), p-isopropylbenzyl alcohol, p,alpha,alpha-trimethylbenzyl alcohol, and p-isopropylbenzaldehyde. 3. The enzymatic products of p-cymene resulted from catalysed enzymatic arene-epoxidation and hydroxylation reactions by the studied cytochrome P450 enzymes. 4. An in vivo study could only confirm the formation of one enzymatic product, namely thymol. Thymol was identified after enzymatic hydrolysis of glucuronide and sulphate conjugates in collected blood and urine samples. 5. The obtained results may help to increase the understanding of cases where skin sensitization and irritation by tea tree oil-containing products that are involved with allergic reactions of users of these products. The results also indicate that skin sensitization and irritation reactions not only can be explained by the frequently in literature reported auto-oxidation of tea tree resulting in bioactive oxidized products, but also now by the formation of epoxide intermediates resulting from catalysed arene-epoxidation reactions by selected human cytochrome P450 enzymes which are also located in different organs in humans.
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Article: Spätfolgen der Überdüngung Editorial
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ABSTRACT: Thymus species have been used for centuries as a folk remedy against cancer. The aim of the present study is to highlight some of the molecular mechanisms involved in the anticancer properties of Thymus pulegioides L. The experiments were performed on male Wistar rats, using the volatile oil from Thymus pulegioides L. The modifications of cytochrome b5 content, cytochromes P450 content and activity, glutathione S-transferase (GST), DT-diaphorase activity and glutathione (GSH) content were evaluated. GC-MS (gas cromatography - mass spectrometry) analysis showed that the main components of Thymus volatile oil were: carvacrol 17.92%, thymol 4.37% and germacrene D 9.84%. The positive effects of Thymus volatile oil could be seen in modifications of the tumors volume and the immune response. An increase was determined in the activity of phase II enzymes, GST and DT-diaphorase, with 75% and 120% respectively. The most remarkable result of this study is the difference in the macroscopic aspects of the tumors, following the administration of Thymus volatile oil, which could recommend it as a chemopreventive agent.Farmacia 01/2011; 59(2):228-238.