Faria Ana, Rosário Monteiro, Diogo Pestana, Victor De Freitas, Nuno Mateus, Isabel Azevedo, Conceição Calhau, "Intestinal Oxidative State Can Alter Nutrient and Drug Bioavailability", Oxidative Medicine and Cellular Longevity, vol. 2, Article ID 928374, 6 pages, 2009. https://doi.org/10.4161/oxim.2.5.9769
Intestinal Oxidative State Can Alter Nutrient and Drug Bioavailability
Organic cations (OCs) are substances of endogenous (e.g., dopamine, choline) or exogenous (e.g., drugs like cimetidine) origin that are positively charged at physiological ph. since many of these compounds can not pass the cell membrane freely, their transport in or out of cells must be mediated by specific transport systems. Transport by organic cation transporters (OCTs) can be regulated rapidly by altering their trafficking and/or affinities in response to stimuli. However, for example, a specific disease could lead to modifications in the expression of OCTs. Chronic exposure to oxidative stress has been suggested to alter regulation and functional activity of proteins through several pathways. According to results from a previous work, oxidation-reduction pathways were thought to be involved in intestinal organic cation uptake modulation. The present work was performed in order to evaluate the influence of oxidative stressors, especially glutathione, on the intestinal organic cation absorption. For this purpose, the effect of compounds with different redox potential (glutathione, an endogenous antioxidant, and procyanidins, diet antioxidants) was assessed on MPP+ (1-methyl-4-phenylpyridinium iodide) uptake in an enterocyte cell line (Caco-2). Caco-2 cells were subcultured with two different media conditions (physiological: 5 mM glucose, referred as control cells; and high-glucose: 25 mM glucose, referred as HG cells). In HG cells, the uptake was significantly lower than in control cells. Redox changing interventions affected Mpp+ uptake, both in control and in high-glucose Caco-2 cells. Cellular glutathione levels could have an important impact on membrane transporter activity. The results indicate that modifications in the cellular oxidative state modulate MPP+ uptake by Caco-2 cells. Such modifications may reflect in changes of nutrient and drug bioavailability.
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