title: Modulation of MPP+ uptake by procyanidins in Caco-2 cells: involvement of oxidation/reduction reactions.
abstract: It is becoming increasingly evident that the absorption of certain nutrients and drugs and their effects are largely influenced by the concomitant ingestion of other substances. As various xeno- and endobiotics belong to the class of organic cations, the aim of this work was to study the modulation of the intestinal apical uptake of organic cations by diet procyanidins. Five procyanidin fractions with different structural complexity were obtained after fractionation of a grape seed extract. The effect of these compounds on 1-methyl-4-phenylpyridinium (MPP+) uptake was evaluated in Caco-2 cells. Apical uptake of 3H-MPP+ by Caco-2 cells was increased by a 60 min exposure to 600 microg ml(-1) of procyanidin fractions, that increase being positively related with procyanidins structural complexity. It was verified that 3H-MPP+ uptake increased with preincubation time. It was speculated that procyanidins were oxidized during preincubation, this change could interfered with transport activity. Tested oxidizing agents showed that the redox state of the transporter could affect its activity. Additionally, trans-stimulation experiments showed that catechin and fraction I (the simpler fraction) can use the same transporter as MPP+. The results are compatible with the hypothesis of these compounds being competitive inhibitors of MPP+ transport. In conclusion, procyanidins are capable to modulate MPP+ apical uptake in Caco-2 cells, this transport being most probably modulated through oxidation-reduction phenomena. Interactions between these compounds and drugs present in the diet may affect their absorption and bioavailability. Both the concentration and complexity of the procyanidin compounds should be taken into account in medical practice.
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine of the University of Porto, Al. Prof. Hernani Monteiro, 4200-319 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Faria
authors.forename: Nuno
authors.initials: N
authors.lastname: Mateus
authors.forename: Vítor
authors.initials: V
authors.lastname: de Freitas
authors.forename: Conceição
authors.initials: C
authors.lastname: Calhau
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism* / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D044946:Biflavonoids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D018938:Caco-2 Cells; D002392:Catechin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002412:Cations / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D006540:Herbicides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D044945:Proanthocyanidins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D044946:Biflavonoids; D002412:Cations; D006540:Herbicides; D044945:Proanthocyanidins; D015262:Xenobiotics; C017674:procyanidin; D002392:Catechin; D015655:1-Methyl-4-phenylpyridinium