THE INFLUENCE OF METHANANDAMIDE AND SEX ON THE ACTIVITY OF CYTOCHROME P 450 AS A PREDICTIVE FACTOR OF XENOBIOTICS TOXICITY
| Authors | |
|---|---|
| Year of publication | 2007 |
| Type | Article in Periodical |
| Magazine / Source | Chemické listy |
| MU Faculty or unit | |
| Citation | |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | (R)-(+)-Methanandamide/ cytochrome P 450/ isolated perfused rat liver/ sex difference |
| Description | The primary active constituent of the hemp plant Cannabis sativa is 9-tetrahydrocannabinol (THC)1. Anandamide, an endogenous ligand for brain cannabinoid CB1 receptor, produces many behavioural effects similar to those of THC. (R)-(+)-methanandamide (MET) is a synthetic long-lasting arachidonylethanolamide (anandamide) analogue. The enzymatic system of cytochrome P450 (CYP450) is part of phase I of enzymatic biotransformation. Interindividual variability of activity of oxidative and conjugating enzymes, especially the system of CYP450, can be based on many exogenous as well as endogenous influences e.g. sex, age or genetic factors. The aim of this work was to investigate the effect of repeated administration of (MET) on rat liver CYP2D2 isoenzyme using dextromethorphan (DEM) as a specific marker4. We have also studied the role of sex on the activity of CYP2D2 isoenzyme. The activity of CYP2D2 differed due to pretreatment with methanandamide. In our experiments the influence of this compound on rat CYP2D2 was inhibitive and metabolic activity of studied isoenzyme CYP2D2 in male and female rats was significantly higher in the control group than in (MET). The levels of metabolite DOR in the pre-treated R-MG groups of rats were lower than in controls of both sexes. |
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