alexa Resveratrol transport and metabolism by human intestinal Caco-2 cells.
Biomedical Sciences

Biomedical Sciences

Biology and Medicine

Author(s): Kaldas MI, Walle UK, Walle T

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Abstract Resveratrol is a dietary constituent suggested to have protective effects against cancer as well as cardiovascular disease. The purpose of the study was to learn whether this agent could be absorbed in man and enter the systemic circulation. This was examined by measuring transport and metabolism of resveratrol (5-40 microM) by the human intestinal epithelial cell line Caco-2 cultured in Transwells. Transport across the Caco-2 monolayer occurred in a direction-independent manner with P(app) values of approximately 7 x 10(-6) cm s(-1), much higher than for the paracellular transport marker mannitol (approximately 0.4 x 10(-6) cm s(-1)), suggesting efficient absorption in-vivo. At the highest resveratrol concentration, the absorption increased, possibly due to saturation of metabolism. In sharp contrast to previous findings in the rat, the metabolism of resveratrol in Caco-2 cells involved mainly sulfation and, to a minor extent, glucuronidation. At low resveratrol concentrations, most of the sulfate conjugate was exported to the apical side, presumably by MRP2, which is well expressed in these cells. At high concentrations, there was a shift towards the basolateral side, possibly involving MRP3, which was recently shown also to be expressed in Caco-2 cells. These results indicate that absorption of resveratrol in-vivo may be high but with limited bioavailability due to efficient sulfate conjugation. Extensive accumulation of resveratrol in the Caco-2 cells, demonstrated in additional experiments, suggests enterocytes as a major target site for this cancer preventive agent. This article was published in J Pharm Pharmacol and referenced in Biology and Medicine

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