Hostname: page-component-7479d7b7d-pfhbr Total loading time: 0 Render date: 2024-07-13T05:42:55.489Z Has data issue: false hasContentIssue false
  • English
  • Français

Dietary flavonoids as intracellular substrates for an erythrocyte trans-plasma membrane oxidoreductase activity

Published online by Cambridge University Press:  08 March 2007

Mara Fiorani  and
Augusto Accorsi
Mara Fiorani*
Affiliation:
Istituto di Chimica Biologica ‘Giorgio Fornaini’, Università degli Studi di Urbino, Via Saffi 2, 61029 Urbino, (PU), Italy
Augusto Accorsi
Affiliation:
Istituto di Chimica Biologica ‘Giorgio Fornaini’, Università degli Studi di Urbino, Via Saffi 2, 61029 Urbino, (PU), Italy
*
*Corresponding author: Dr Mara Fiorani, fax +39 0722 320188, email m.fiorani@uniurb.it
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The plasma membrane oxidoreductase (PMOR) activity, which mainly utilises ascorbate as intracellular electron donor, represents a major mechanism for cell-dependent reduction of extracellular oxidants and might be an important process used by the erythrocytes to keep a reduced plasma environment. We previously reported that in human erythrocytes, myricetin and quercetin act as intracellular substrates of a PMOR showing a novel mechanism whereby these flavonoids could exert beneficial effects under oxidative stress conditions. Here, we evaluated the ability of different flavonoids (quercetin, myricetin, morin, kaempferol, fisetin, catechin, luteolin, apigenin, acacetin, rutin, taxifolin, naringenin, genistein) and of two in vivoO-methylated metabolites of quercetin (isorhamnetin and tamarixetin) to be substrates of PMOR, by comparing their antioxidant capacity (i.e. direct interaction with the oxidant ferricyanide or with the free radical 1,1-diphenyl-2-picryl-hydrazil) with their ability to penetrate the erythrocytes and donate electrons to the PMOR. The results obtained indicate that, although most of the flavonoids display significant antioxidant activities, only those (quercetin, myricetin, fisetin) that combine the cathecol structure of the B ring (responsible for the reducing activity) with the 2,3 double bond and 4-oxo function of the C ring (responsible for the uptake by erythrocytes) can act as intracellular substrates for PMOR. It is of note that the metabolites of quercetin enter erythrocytes and donate electrons to the PMOR as the parent compound. The present data show a relationship between the flavonoid structures and their ability to provide electrons to the PMOR, suggesting an additional mechanism whereby dietary flavonoids may exert beneficial effects in man.

Keywords

FlavonoidsTrans-plasma membrane oxidoreductaseFerricyanide1,1-Diphenyl-2-picryl-hydrazil
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 3 , September 2005 , pp. 338 - 345
Copyright
Copyright © The Nutrition Society 2005

References

Afanas'ev, IB, Dorozhko, AI, Brodskii, AW, Korstyuk, VA & Potapovich, AI (1989) Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation. Biochem Pharmacol 38, 1763–1768.CrossRefGoogle ScholarPubMed
Avron, M & Shavit, N (1963) A sensitive simple method for determination of ferrocyanide. Anal Biochem, 6, 549–555.CrossRefGoogle ScholarPubMed
Awad, HM, Boersma, MG, Boeren, S, Van Bladeren, J, Vervoort, J & Rietjens, IMCM (2001) Structure-activity study on quinone/quinone methide chemistry of flavonoids. Chem Res Toxicol 14, 398–408.CrossRefGoogle Scholar
Awad, HM, Boersma, MG, Vervoort, J & Rietjens, IMCM (2000) Peroxidase-catalyzed formation of quercetin quinine methide-glutathione adducts. Arch Biochem Biophys 378, 224–233.Google Scholar
Bandonienè, D & Murkovic, M (2002) On line HPLC-DPPH · screening method for evaluation of radical scavenging phenols extracted from apples ( Malus domestica L. ). J Agric Food Chem 50, 2482–2487.CrossRefGoogle ScholarPubMed
Bolton, JL, Pisha, E, Zhang, F & Qiu, S (1998) Role of quinoids in estrogen carcinogenesis. Chem Res Toxicol 11, 1113–1126.CrossRefGoogle ScholarPubMed
Bors, W, Heller, W, Michel, C & Saran, M (1990) Flavonoids as antioxidants: determinations of radical scavenging efficiences. Methods Enzymol 234, 343–355.Google Scholar
Cao, G, Sofic, E & Prior, R (1997) Antioxidant and prooxidant behaviour of flavonoids: structure-activity relationship. Free Rad Biol Med 22, 749–760.CrossRefGoogle Scholar
Day, AJ, Bao, Y, Morgan, MRA & Williamson, G (2000) Conjugation position of quercetin glucuronides and effect on biological activity. Free Rad Biol Med 29, 1234–1243.Google Scholar
Ferrali, M, Signorini, C, Caciotti, B, Sugherini, L, Ciccoli, L, Giacchetti, D & Comporti, M (1997) Protection against oxidative damage of erythrocyte membrane by the flavonoid quercetin and its relation to iron chelating activity. FEBS Lett 416, 123–129.Google Scholar
Fiorani, M, Accorsi, A & Cantoni, O (2003) Human red blood cells as a natural flavonoid reservoir. Free Rad Res 37, 1331–1338.Google Scholar
Fiorani, M, De Sanctis, R, De Bellis, R & Dachà, M (2002) Intracellular flavonoid as electron donors for extracellular ferricyanide reduction in human erythrocytes. Free Rad Biol Med 32, 64–72.CrossRefGoogle ScholarPubMed
Firuzi, O, Lacanna, A, Petrucci, R, Marrosu, G & Saso, L (2005) Evaluation of the antioxidant activity of flavonoids by ‘ferric reducing antioxidant power’ assay and cyclic voltametry. Biochem Biophys Acta 1721, 174–184.Google Scholar
Guglielmone, HA, Agnese, AM, Nunez Montoya, SC & Cabrera, JL (2002) Anticoagulant effect and action mechanism of sulphated flavonoids from Flaveria bidentis. Thromb Res 105, 183–188.Google Scholar
Himmelreich, U & Kuchel, PW (1997) 13 C-NMR studies of transmembrane electron transfer to extracellular ferricyanide in human erythrocytes. Eur J Biochem 246, 638–645.CrossRefGoogle Scholar
Keli, SO, Hertog, MG, Feskens, EJ & Kromhout, D (1996) Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study, Arch Intern Med 156, 637–642.CrossRefGoogle ScholarPubMed
Kennett, EC & Kuchel, PW (2003) Redox reaction and electron transfer across the red cell membrane. IUBMB Life 55, 375–385.Google Scholar
Kroon, PA, Clifford, MN, Day, AJ, Donovan, JL, Manach, C & Williamson, G (2004) How should we assess the effects of exposure to dietary polyphenols in vitro?. Am J Clin Nutr 80, 15–21.Google Scholar
Lee, JC, Park, JK, Chung, GH & Jang, YS (2003) The antioxidant, rather than prooxidant, activities of quercetin on normal cells: quercetin protects mouse thymocytes from glucose oxidase-mediated apoptosis. Exp Cell Res 291, 386–397.Google Scholar
MacGregor, JT & Jurd, L (1978) Mutagenicity of plant flavonoids: structural requirements for mutagenic activity in Salmonella typhimurium. Mutat Res 54, 297–309.CrossRefGoogle ScholarPubMed
Mallors, A & Tappel, AL (1966) The inhibition of mitochondrial peroxidation by ubiquinone and ubiquitol. J Biol Chem 241, 4353–4356.Google Scholar
Manach, C, Williamson, G, Morand, C, Scalbart, A & Remesy, C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 21, 230S–242S.CrossRefGoogle Scholar
May, JM (1999) Is ascorbic acid an antioxidant for the plasma membrane?. FASEB J 13, 995–1006.CrossRefGoogle ScholarPubMed
May, JM, Mendiratta, S, Qu, ZC & Loggins, E (1999) Vitamin C recycling and function in human monocytes U-937 cells. Free Rad Biol Med 26, 1513–1523.CrossRefGoogle ScholarPubMed
May, JM, Qu, ZC & Morrow, JD (1996) Interaction of ascorbate and α-tocopherol in resealed human erythrocyte ghosts. J Biol Chem 271, 10577–10582.CrossRefGoogle ScholarPubMed
Ness, AR & Powles, JW (1997) Fruits, vegetables and cardiovascular disease: a review. Int J Epidemiol 26, 1–13.CrossRefGoogle ScholarPubMed
Penning, TM, Burczynski, ME, Hung, CF, McCoull, KD, Palackal, NT & Tsuruda, LS (1999) Dihydrodiol dehydrogenases and polycyclic aromatic hydrocarbon activation: generation of reactive and redox active o-quinones. Chem Res Toxicol 12, 1–18.CrossRefGoogle ScholarPubMed
Rice-Evans, CA, Miller, NJ & Paganga, G (1997) Antioxidant properties of phenolic compounds. Trends Plant Sci 2, 152–159.Google Scholar
Richter, M, Ebermann, R & Marian, B (1999) Quercetin-induced apoptosis in colorectal tumor cells: possible role of EGF receptor signaling. Nutr Cancer 34, 88–99.Google Scholar
Ross, AJ & Kasum, CM (2002) Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22, 19–34.CrossRefGoogle ScholarPubMed
Sahu, SC & Washington, MC (1991) Quercetin-induced lipid peroxidation and DNA damage in isolated rat-liver nuclei. Cancer Lett 58, 75–79.CrossRefGoogle ScholarPubMed
Schroeter, H, Boyd, CS, Ahmed, R, Spencer, JPE, Duncan, RF, Rice-Evans, C & Cadenas, E (2003) c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK signalling in mitochondrion-dependent apoptosis. Biochem J 372, 359–369.CrossRefGoogle ScholarPubMed
Spencer, JPE, Abd-El-Mohsen, MM & Rice-Evans, C (2004) Cellular uptake and metabolism of flavonoids and their metabolites: implication for their bioactivity. Arch Biochem Biophys 423, 148–161.Google Scholar
Spencer, JPE, Kuhnle, G, Williams, RJ & Rice-Evans, C (2003a) Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. Biochem J 372, 173–181.CrossRefGoogle ScholarPubMed
Spencer, JPE, Rice-Evans, C & Williams, RJ (2003b) Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viabilityM. J Biol Chem 278, 34783–34793.Google Scholar
Spencer, JPE, Schroeter, H, Crossthwaithe, AJ, Kuhnle, G, Williams, RJ & Rice-Evans, C (2001a) Contrasting influences of glucuronidation and O -methylation of epicatechin on hydrogen peroxide-induced cell death in neurons and fibroblasts. Free Rad Biol Med 31, 1139–1146.CrossRefGoogle Scholar
Spencer, JPE, Schroeter, H, Kuhnle, G, Srai, SK, Tyrrell, RM, Hahn, U & Rice-Evans, C (2001b) Epicatechin and its in vivo metabolite, 3'-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase-3 activation. Biochem J 345, 493–500.CrossRefGoogle Scholar
Steinmetz, KA & Potter, JD (1991a) Vegetables, fruit and cancer I. Epidemiology. Cancer Causes Control 5, 325–337.CrossRefGoogle Scholar
Steinmetz, KA & Potter, JD (1991b) Vegetables, fruit and cancer II. Mechanisms. Cancer Causes Control 5, 427–442.Google Scholar
Tukey, RH & Strassburg, CP (2000) Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40, 581–616.Google Scholar
Van Duijn, MM, van den Zee, J, VanSteveninck, J & van den Broek, PJA (1998) Ascorbate stimulates ferricyanide reduction in HL-60 cells through a mechanism distinct from the NADH-dependent plasma membrane reductase. J Biol Chem 273, 13415–13420.Google Scholar
Van Dyke, BR & Saltman, P (1996) Hemoglobin: a mechanism for the generation of hydroxyl radicals. Free Rad Biol Med 20, 985–989.CrossRefGoogle ScholarPubMed
Williams, RJ, Spencer, JPE & Rice Evans, C (2004) Flavonoids: antioxidants or signaling molecules?. Free Rad Biol Med 7, 838–849.Google Scholar