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 3 H-MPP + by Caco-2 cells was increased by a 60 min exposure to 600 lg ml À1 of procyanidin fractions, that increase being positively related with procyanidins structural complexity. It was verified that 3 H-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.

Impact of culture media glucose levels on the intestinal uptake of organic cations

“…Altogether, these results are compatible with a modulation of organic cation transport in Caco-2 cells through redox mechanisms, as has been previously advanced (Faria et al 2006).…”

Prodelphinidins isolated from Chinese bayberry leaves induces apoptosis via the p53-dependent signaling pathways in OVCAR-3 human ovarian cancer cells

“…In the present study OPAs and PPAs exhibited strong effects on OVCAR-3 cell proliferation and apoptosis. Several studies have reported evidence that monomeric catechins and proanthocyanidin monomers, dimers and trimers can be absorbed through human intestinal Caco-2 epithelial cells (24,25). However, the results of the present study revealed that PPAs (prodelphinidin tetramers and higher polymerizations) exerted greater cytotoxic and apoptotic activities compared with OPAs (dimers and trimers) in general.…”

Liquid chromatography tandem mass spectrometry identification of proanthocyanidins in rat plasma after oral administration of grape seed extract

“…However, studies by Holt et al (2002) demonstrated the presence of dimeric procyanidins in human plasma as early as 30 min after the consumption of a flavanol-rich food such as cocoa. There is evidence in support of absorption of monomeric catechins and proanthocyanidins through the human intestinal caco-2 epithelial cells (Deprez et al, 2001; Faria et al, 2006). Another study by Tsang et al (2005) reported the absorption and metabolism of catechin and proanthocyanidins up to trimers in urine following the oral intake of GSE.…”