Bioscience Horizons Advance Access published online on May 2, 2008
Bioscience Horizons, doi:10.1093/biohorizons/hzn021
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© Oxford University Press 2008
The potential effect of excessive coffee consumption on nicotine metabolism: CYP2A6 inhibition by caffeic acid and quercetin
Faculty of Sciences, Staffordshire University, College Road, Stoke on Trent, Staffordshire ST4 2DE, UK
* Corresponding author: Diet and health group, Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, NR4 7TJ, UK. Tel: +44 (0)7746144623. Email: g.woodward{at}uea.ac.uk
Supervisor: Dr Susan Bird, Faculty of Sciences, Staffordshire University, College Road, Stoke on Trent, Staffordshire ST4 2DE, UK.
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Abstract |
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Over the past decade interest in the biochemical and biological properties of polyphenols has grown considerably, as epidemiological evidence for their beneficial effects on health continues to increase. Dietary polyphenol antioxidants are reported to have many ‘health promoting’ properties, including anti-inflammatory, vasoprotection, anti-cancer and anti-obesity effects. However, their absorption and metabolism are as yet not fully elucidated, particularly with regard to their interactions with other metabolized compounds, such as nicotine. Epidemiological studies have shown that coffee-drinking cigarette smokers are more likely to smoke less in comparison to non-coffee drinking cigarette smokers. Nicotine is primarily metabolized by the hepatic cytochrome P450 enzyme CYP2A6 and may be inhibited by the metal chelating properties of polyphenols via haem interactions with their hydroxyl groups. To model nicotine metabolism, bovine liver microsomes, shown to suitably represent human CYP2A6 metabolism, were isolated by calcium precipitation and differential centrifugation. Fluorometric analysis of 7-hydroxycoumarin, the CYP2A6 metabolite of coumarin and known probe for CYP2A6 activity, was used to model nicotine metabolism in vitro and to quantify the degree of CYP2A6 inhibition imposed by caffeic acid and quercetin. It was found that both caffeic acid and quercetin, major polyphenolic constituents of caffeine containing beverages, significantly inhibited CYP2A6 activity in vitro by 37.9% (P < 0.05) and 48.2% (P < 0.05), respectively. Thus, this study demonstrates the first reported biochemical evidence in support of previous epidemiological observations, where it is suggested that polyphenol interaction with CYP2A6 prolongs the pharmacological effects of nicotine by decreasing its rate of elimination.
Key words: polyphenols, CYP2A6, caffeic acid, quercetin, nicotine
Submitted on 20 September 2007; accepted on 28 January 2008