Inhibition and induction of human cytochrome P450 enzymes in vitro by capsaicin.
Summary of "Inhibition and induction of human cytochrome P450 enzymes in vitro by capsaicin."
Widespread exposure to capsaicin occurs through food and topical medicines. To investigate potential food-drug or drug-drug interactions, capsaicin was evaluated in vitro against seven human drug-metabolizing cytochrome P450 (CYP) enzymes. At concentrations occurring after ingestion of chili peppers or topical administration of a high-concentration patch, capsaicin did not cause direct inhibition of any CYP enzyme. Direct inhibition was only observed at much higher concentrations; the lowest IC(50) value was 2.0 μM. For CYP2E1, the IC(50) value was too high to calculate. With pre-incubation, inhibition decreased for CYP1A2, 2C9, 2C19 and 3A4/5, whereas inhibition of CYP2B6 increased and moderately increased for CYP2D6. Induction of CYP activity was evaluated in microsomes from hepatocyte primary cultures. Capsaicin did not induce CYP1A2, 2B6, 2C9, 2C19, 2E1 or 3A4/5. 10 μM capsaicin caused a statistically significant increase in CYP1A2 activity (8.6% of the positive control). Inhibition of drug metabolism by capsaicin should be minimal, as the ratio of [I]/K(i) for direct inhibition is < 0.1. Although pre-incubation did enhance the potency for CYP2B6 inhibition to 5.1 μM, given that exposure to capsaicin from either food or a topical medicine is very low (≤58 nM) and transient, effects on CYPs appear unlikely.
Affiliation
NeurogesX, Inc., San Mateo, California, USA.
Journal Details
This article was published in the following journal.
Name: Xenobiotica; the fate of foreign compounds in biological systems
ISSN: 1366-5928
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20863199
- DOI: http://dx.doi.org/10.3109/00498254.2010.520044
Medical and Biotech [MESH] Definitions
Metabolic Detoxication, Phase I
Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS.
Pregnenolone Carbonitrile
A catatoxic steroid and microsomal enzyme inducer having significant effects on the induction of cytochrome P450. It has also demonstrated the potential for protective capability against acetaminophen-induced liver damage.
Cytochrome P-450 Cyp27a1
An NAPH-dependent cytochrome P450 enzyme that catalyzes the oxidation of the side chain of sterol intermediates such as the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha, 12-alpha-triol. Cytochrome P-450 CYP27A1 is a mitochondrial enzyme; however microsomal-derived homologs of the enzyme have been identified and are included under this heading.
Cytochrome P-450 Cyp2d6
A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population.
Cytochrome P-450 Cyp1a2
A cytochrome P-450 monooxygenase that can be induced by polycyclic aromatic xenobiotics in the liver of human and several animal species. This enzyme is of significant clinical interest due to the large number of drug interactions associated with its induction and its metabolism of THEOPHYLLINE. Caffeine is considered to be a model substrate for this enzyme. CYP1A2 activity can also be increased by environmental factors such as cigarette smoking, charbroiled meat, cruciferous vegetables, and a number of drugs including phenytoin, phenobarbital, and omeprazole.
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