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2002 | 49 | 4 | 917-925
Article title

Effect of natural phenols on the catalytic activity of cytochrome P450 2E1

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The effect of protocatechuic acid, tannic acid and trans-resveratrol on the activity of p-nitrophenol hydroxylase (PNPH), an enzymatic marker of CYP2E1, was examined in liver microsomes from acetone induced mice. trans-Resveratrol was found to be the most potent inhibitor (IC50 = 18.5 ± 0.4 mM) of PNPH, while protocatechuic acid had no effect on the enzyme activity. Tannic acid with IC50 = 29.6 ± 3.3 mM showed mixed- and trans-resveratrol competitive inhibition kinetics (Ki = 1 mM and 2.1 mM, respectively). Moreover, trans-resveratrol produced a NADPH-dependent loss of PNPH activity, suggesting mechanism-based CYP2E1 inactivation. These results indicate that trans-resveratrol and tannic acid may modulate cytochrome P450 2E1 and influence the metabolic activation of xenobiotics mediated by this P450 isoform.
Physical description
  • Department of Pharmaceutical Biochemistry, University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland
  • Department of Pharmaceutical Biochemistry, University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland
  • Department of Pharmaceutical Biochemistry, University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland
  • Baer-Dubowska W, Gnojkowski J, Fenrych W. (1997) Effect of tannic acid on benzo[a]pyrene-DNA adduct formation in mouse epidermis: comparison with synthetic gallic acid esters. Nutr Cancer.; 29: 42-7.
  • Baer-Dubowska W, Szaefer H, Krajka-Kuzniak V. (1998) Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds. Xenobiotica.; 28: 735-43.
  • Burns J, Yokota T, Ashihara H, Lean MEJ, Crozier A. (2002) Plant foods and herbal sources of resveratrol. J Agric Food Chem.; 50: 3337-40.
  • Cai Y, Bennett D, Nair RV, Ceska O, Ashwood-Smith MJ, DiGiovanni J. (1993) Inhibition and inactivation of murine hepatic ethoxy- and pentoxyresorufin O-dealkylase by naturally occurring coumarins. Chem Res Toxicol.; 6: 872-9.
  • Chang TKH, Lee WBK, Ko HH. (2000) Trans-resveratrol modulates the catalytic activity and mRNA expression of the procarcinogen-activating human cytochrome P450 1B1. Can J Physiol Pharmacol.; 78: 874-81.
  • Chang TKH, Yeung RKY. (2001) Effect of trans-resveratrol on 7-benzyloxy-4-trifluoromethylcoumarin O-dealkylation catalyzed by human recombinant CYP3A4 and CYP3A5. Can J Physiol Pharmacol.; 79: 220-26.
  • Chang TKH, Chen J, Lee WBK. (2001) Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2. J Pharmacol Exp Ther.; 299: 874-82.
  • Chen S-C, Chung K-T. (2000) Mutagenicity and antimutagenicity studies of tannic acid and its related compounds. Food Chem Toxicol.; 38: 1-5.
  • Chun YJ, Kim, MY, Guengerich P. (1999) Resveratrol is a selective human cytochrome P450 1A1 inhibitor. Biochem Biophys Res Commun.; 262: 20-4.
  • Ciolino HP, Daschner PJ, Yeh GC. (1998) Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of aryl hydrocarbon receptor. Cancer Res.; 58: 5707-12.
  • Das DK, Sato M, Ray PS, Maulik G, Engelman RM, Bertelli AA, Bertelli A. (1999) Cardioprotection of red wine: role of polyphenolic antioxidants. Drugs Exp Clin Res.; 25: 115-20.
  • Geahlen RL, McLaughlin JL. (1989) Isolation of piceatannol as the antileukemic principle from the seeds of euphorbia lagascae. Biochem Biophys Res Commun.; 165: 241-45.
  • Gnojkowski J, Baer-Dubowska W, Klimek D, Chmiel J. (1984) Effect of toluidines on drug metabolizing enzymes. Toxicology.; 32: 335-42.
  • Guengerich FP, Kim DH, Iwasaki M. (1991) Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol.; 4: 168-79.
  • Guengerich FP, Shimada T. (1998) Activation of procarcinogens by human cytochrome P450 enzymes. Mutat Res.; 400: 201-213.
  • Gusman J, Malonne H, Atassi G. (2001) A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol. Carcinogenesis.; 22: 1111-17.
  • Guyonnet D, Belloir C, Suschetet M, Siess M-H, Le Bon A-M. (2000) Liver subcellular fractions from rats treated by organosulfur compounds from Allium modulate mutagen activation. Mutat Res.; 466: 17-26.
  • Hursting SD, Slaga TJ, Fisher SM, DiGiovanni J, Phang JM. (1999) Mechanism-based cancer approaches: targets, examples, and use of transgenic mice. J Natl Cancer Inst.; 91: 215-25.
  • Ignatowicz E, Baer-Dubowska W. (2001) Resveratrol, a natural chemopreventive agent against degenerative diseases. Pol J Pharmacol.; 53: 557-69.
  • Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HHS, Farnsworth NR, Kinghorn DA, Mehta RG, Moon RC, Pezzuto JM. (1997) Cancer chemopreventive activity of resveratrol, a nature product derived from grapes. Science.; 275: 218-20.
  • Kobayashi K, Urashima K, Shimada N, Chiba K. (2002) Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with cDNA-expressed systems of the rat. Biochem Pharmacol.; 63: 889-96.
  • Koop DR, Laethem CL, Tierney DJ. (1989) The utility of p-nitrophenol hydroxylation in P450IIE1 analysis. Drug Metab Rev.; 20: 541-51.
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. (1951) Protein measurement with the Folin phenol reagent. J Biol Chem.; 193: 230-65.
  • Li ZG, Hong T, Shimada Y, Komoto I, Kawabe A, Ding Y, Kaganoi J, Hashimoto Y, Imamura M. (2002) Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol. Carcinogenesis.; 23: 1531-6.
  • Mori H, Matsunaga K, Tanakamaru Y, Kawabata K, Yamada Y, Sugie S, Nishikawa A. (1999) Effects of protocatechuic acid, S-methylmethanethiosulfonate or 5-hydroxy- 4-(2-phenyl-(E)ethenyl)-2(5H)-furanone (KYN-54) on 4-(methylnitrosoamino)-1-(3- pyridyl)-1-butanone-induced pulmonary carcinogenesis in mice. Cancer Lett.; 135: 123-27.
  • Nakajima M, Yoshida R, Shimada N, Yamazaki H, Yokoi T. (2001) Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate. Drug Metab Dispos.; 29: 1110-3.
  • Nakamura H, Nishikawa A, Furukawa F, Kasahara K, Miyauchi M, Son H-Y, Hirose M. (2000) Inhibitory effects of protocatechuic acid on the post-initiation phase of hamster pancreatic carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine. Anticancer Res.; 20: 3423-7.
  • Nepka C, Asprodini E, Kouretas D. (1999) Tannins, xenobiotic metabolism and cancer chemoprevention in experimental animals. Eur J Drug Metab Pharmacokinet.; 24: 183-9.
  • Newmark HL. (1987) Plant phenolics as inhibitors of mutational and precarcinogenic events. Can J Physiol Pharmacol.; 65: 461-6.
  • Ohnishi M, Yoshimi N, Kawamori T, Ino N, Hirose Y, Tanaka T, Yamahara J, Miyata H, Mori H. (1997) Inhibitory effects of dietary protocatechuic acid and costunolide on 7,12-dimethylben[a]anthracene-induced hamster cheek pouch carcinogenesis. Jpn J Cancer Res.; 88: 111-9.
  • Piver B, Berthou F, Dreano Y, Lucas D. (2001) Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett.; 125: 83-91.
  • Potter GA, Patterson LH, Wanogho E, Perry PJ, Butler PC, Iliaz T, Ruparelia KC, Lamb JH, Farmer PB, Stanley LA, Burke MD. (2002) The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1. Br J Cancer.; 86: 774-8.
  • Reinke LA, Moyer MJ. (1985) p-Nitrophenol hydroxylation - a microsomal oxidation which is highly inducible by ethanol. Drug Metab Dispos.; 13: 548-52.
  • Soleas GJ, Diamandis EP, Golberg DM. (1997) Wine as a biological fluid: history, production, and role in disease prevention. J Clin Lab Anal.; 11: 287-313.
  • Soleas GJ, Grass L, Josephy PD, Goldberg DM, Eleftherios P. (2002) A comparison of the anticarcinogenic properties of four wine poly phenols. Clin Biochem.; 35: 119-24.
  • Sporn MB, Suh N. (2000) Chemoprevention of cancer. Carcinogenesis.; 21: 525-30.
  • Uenobe F, Nakamura S, Miyazawa M. (1997) Antimutagenic effect of resveratrol against Trp-P-1. Mutat Res.; 373: 197-200.
  • Voet D, Voet JG. (1995) Rates of enzymatic reactions. In Biochemistry. Ardwin L, Ingrao S. eds, pp 355-60, John Wiley & Sons, Inc., New York.
  • Yang CS, Smith TJ, Hong J-Y. (1994) Cytochrome P450 enzymes as targets for chemoprevention against chemical carcinogenesis and toxicity: opportunities and limitations. Cancer Res (Suppl).; 54: 1982s-6s.
  • Yun C-H, Jhoun JW, Guengerich FP. (1995) Non-specific inhibition of cytochrome P450 activities by chlorophyllin in human and rat liver microsomes. Carcinogenesis.; 16: 1437-40.
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