The Effect of (-)-Linalool on the Metabolic Activity of Liver CYP Enzymes in Rats

Abstract

(-)-Linalool is the major floral scent occurring mainly in families Lamiaceae, Lauraceae and Rutaceae and is the main active compound of lavender oil. The purpose of this study was to reveal the influence of subchronic systemic treatment with (-)-linalool on the metabolic activity of CYP2A, 2B, 2C6, 2C11 and 3A in rat liver microsomes (RLM). The second aim was to reveal possible inhibitory effect of (-)-linalool on CYP2C6 in vitro. Wistar albino male rats were treated with (-)-linalool intragastrically at the doses of 40, 120, and 360 mg/kg/day for 13 days. Treatment with (-)-linalool at the dose of 360 mg/kg increased the metabolic activity of CYP2A assessed with testosterone as a probe substrate. (-)-Linalool showed weak competitive inhibition of CYP2C6 in rat liver microsomes, with IC50 of 84 μM with use of diclofenac as a probe substrate.

Essential oil components and cytochrome P450 enzymes: a review

“…Although often similar results are obtained with liver cells of both species, there exist inter-species differences regarding the action of potential inhibitors towards individual enzymes or low homology in amino acid sequence of CYP enzymes. 30 This demonstrates a certain limitation concerning drug interaction studies in experimental animals. 41,73 Furthermore, rats were often treated with CYP gene inducers, such as β-naphthoflavone (inducer of the CYP1A subfamily), phenobarbital (inducer of CYP2B1), or 3-methylcholanthrene (3-MC) (inducer of CYP1), to raise the level of the CYP isoenzymes in order to get significant results more easily, which may influence the outcomes.…”

“…aflatoxin B1, cyclophosphamide, 4-(methylnitrosamino)-1-(3-pyridyl)-1 -butanone, nicotine-derived nitrosamine ketone (NNK)], the induction of these CYP enzymes by EO constituents like (-)-linalool can increase the likelihood of cancer, whereas EO constituents such as citral, geraniol, or β-myrcene that inhibit these CYP isoforms may be useful as chemopreventive agents. [29][30][31] Supporting this proposition, the results of an interesting study indicated that dietary Zataria multiflora EOs show colon chemopreventive properties by the modulation of CYP enzymes. 32 On the other hand, this also means that EO constituents like the structurally related alkylbenzenes estragole, safrole, or methyleugenole can be activated to their proximate carcinogens by CYP-inducing factors.…”

“…On the other hand, it was found that CYP2A can metabolically activate a number of carcinogens, including nitrosamines and aflatoxins, and therefore the induction of CYP2A activity should be regarded with caution. 30 Another study, screening for the inhibition of CYP2B6, showed a slight inhibition by linalool. Pooled human liver microsomes that were incubated with linalool showed only about 50% activity of CYP2B6-catalysed bupropion hydroxylation.…”

“…CYP2A, where 2 denotes the family, A denotes the subfamily, and finally a further numeral refers to the first, second, or third, etc., enzyme) can contribute to the activation of procarcinogens [e.g. aflatoxin B1, cyclophosphamide, 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone, nicotine‐derived nitrosamine ketone (NNK)], the induction of these CYP enzymes by EO constituents like (–)‐linalool can increase the likelihood of cancer, whereas EO constituents such as citral, geraniol, or β‐myrcene that inhibit these CYP isoforms may be useful as chemopreventive agents . Supporting this proposition, the results of an interesting study indicated that dietary Zataria multiflora EOs show colon chemopreventive properties by the modulation of CYP enzymes .…”

Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes in In Vitro and In Vivo Models

“…Ibuprofen was used as the internal standard, and the incubation time was 20 minutes. The separation conditions for diclofenac and 49-hydroxydiclofenac determination have been described in detail previously (Noskova et al, 2016).…”