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United States Department of Agriculture

Agricultural Research Service

Title: Intracellular Accumulation of Ascorbic Acid Is Inhibited by Flavonoids Via Blocking of Dehyohroascorbic Acid and Ascorbic Acid Uptakes in Hl-60, U937, and Jarkat Cells.

Authors
item Park, Jae
item Levine, Mark - NIH, NIDDK

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 15, 2000
Publication Date: N/A

Interpretive Summary: Flavonoids are a group of phytonutrients that have been unceasingly investigated to determine their biological functions in vitro and in vivo. A variety of biological effects on human health have been suggested. Past studies of flavonoids have not assessed possible interactions between flavonoids and nutrients, thus not considering their potential impact on each other. In particular, the effect of flavonoids on the uptake of vitamin C has not been investigated in detail even though interactions between flavonoids and vitamin C have been suspected. Therefore the interactive effect of flavonoids on dehydroascorbic acid (an oxidized metabolite of vitamin C) and vitamin C transport was investigated in human cell lines (HL-60, U937, and Jurkat cells). At flavonoid concentrations of 10-70 umol/L, approximately 50% of dehydroascorbic acid uptake was inhibited in the cells. In Jurkat cells, two potent flavonoids (myricetin and quercetin) competitively and strongly inhibited dehydroascorbic acid uptake. Because some glucose transporters (GLUT 1 and GLUT 3) transport dehydroascorbic acid, the inhibition of dehydroascorbic acid uptake by flavonoids was investigated using Chinese hamster ovary cells over- expressing GLUT 1 or GLUT 3. Myricetin strongly inhibited dehydroascorbic acid uptake in the cells over-expressing GLUT 1 and GLUT 3. Myricetin also inhibited vitamin C uptake; inhibition was noncompetitive and strong. These data indicate that flavonoids inhibit both ascorbic acid and dehydroascorbic acid transport but do so by different mechanisms. These data may provide a reference guide for true bioavailability of vitamin C and dietary flavonoids for nutritionists, epidemiologists, and scientists who will determine optimal dietary allowances of vitamin C and flavonoids.

Technical Abstract: In HL-60, U937, and Jurkat cells, the intracellular accumulation of ascorbic acid occurred via uptakes of both dehydroascorbic acid (an oxidized metabolite of ascorbic acid) and ascorbic acid (vitamin C). Dehydroascorbic acid and ascorbic acid were transported into cells by sodium-independent glucose transporters (GLUT 1 and GLUT 3) and sodium- dependent ascorbic acid transporters, respectively. Flavonoids inhibited the intracellular accumulation of ascorbic acid by blocking dehydroascorbic acid and ascorbic acid uptakes in the transformed cells. At flavonoid concentrations of 10-70 umol/L, approximately 50% of dehydroascorbic acid uptake was inhibited in the cells. In Jurkat cells, two potent flavonoids (myricetin and quercetin) competitively inhibited dehydroascorbic acid uptake, and Ki values were approximately 14 and 15 umol/L, respectively. Because GLUT 1 and GLUT 3 transport dehydroascorbic acid, the inhibition of dehydroascorbic acid uptake by flavonoids was investigated by using Chinese hamster ovary cells overexpressing rat GLUT 1 or human GLUT 3. Myricetin at concentrations of 22 and 18 umol/L, respectively, inhibited half of dehydroascorbic acid uptake in the cells overexpressing GLUT 1 and GLUT 3. Myricetin also inhibited ascorbic acid uptake; inhibition was noncompetitive with Ki = 14 umol/L in Jurkat cells. These data indicate that flavonoids inhibit both ascorbic acid and dehydroascorbic acid transport but do so by different mechanisms. These data may contribute to new understanding of the biological effect of flavonoids on the intracellular accumulation of ascorbic acid in human cells.

Last Modified: 10/1/2014
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