Carcinogen Metabolizing Enzymes: Modulation of Their Activities in Liver, Lung and Stomach by Thymoquinone

Background: Thymoquinone (TQ), the bioactive constituent of black seed (Nigella sativa), has been shown to inhibit the growth of various human cancerous cells both in vitro and in vivo.

Aim: To characterize the effects of thymoquinone on the activity of phase I and phase II carcinogen metabolizing enzymes in rats.

Materials and Methods: Phase I enzymes, namely the cytochrome P450 enzymes CYP1A1 and CYP2E1, and phase II enzymes, including UDP-glucuronyltransferase (UGT) and glutathione S-transferase (GST), were studied in the liver, lung and stomach of female Swiss albino rats. The animals were divided into two groups (10 rats/group), a control group treated with corn oil and a TQ-treated group receiving oral (gavage) thymoquinone at a dose of 10 mg/kg/day for 15 consecutive days. Animals were then sacrificed on day 16. Tissue homogenates of liver, lung and stomach were prepared to evaluate the activities of both phase I and phase II selected enzymes.

Results: Thymoquinone treatment induced significant modulation of the selected phase I and phase II enzymes in a tissue-specific manner. Our results revealed statistically significant reductions in the activities of CYP1A1 enzyme (46%, 60% and 57% in liver, lung and stomach respectively) versus the control group. Similarly, CYP2E1 activities were decreased in both liver and lung, by 51% and 16%, respectively, compared to the control group. UGT enzyme showed a decrease of 51% in liver, but a significant rise in both lung and stomach, by 40% and 192%, respectively. GST activity, on the other hand, was moderately enhanced, by 24%, 50% and 30% in liver, lung and stomach, respectively.

Conclusion: Thymoquinone, in addition to scavenging active metabolites of chemical carcinogens, may also change their metabolisms by modulating the activity levels of enzymes involved in carcinogen activation and/or xenobiotics pathways.