Concentration-dependent effects of resveratrol and metabolites on the redox status of human erythrocytes in single-dose studies

Dietary trans-resveratrol (RES) is rapidly metabolized into sulfated and glucuronated conjugates in humans. This study focused on the in vitro determination of the antioxidant capacity of RES and its main physiological metabolites and on its relevance in vivo. In vitro, RES, RES-3- O-sulfate (R3S) and 3- O-glucuronide (R3G) showed antioxidant activities at a concentration of 1 mM when compared to Trolox using an assay in which the antioxidant inhibits iron-induced linoleic acid oxidation: 0.87±0.08 mM Trolox equivalents (TE) for RES, 0.52±0.01 mM TE for R3S and 0.36±0.02 mM TE for R3G. At a concentration of 1 μM, compounds promoted linoleic acid peroxidation (RES -0.30±0.09 mM TE, R3S -0.48±0.05 mM TE and R3G -0.57±0.07 mM TE). To elucidate whether these effects were reflected in vivo, total antioxidant capacity, reactive oxygen species (ROS), conjugated fatty acid dienes (CD), superoxide dismutase (SOD) and catalase (CAT) activities were determined in human plasma and erythrocytes over 24 h, after oral intake of either 0.05 g RES as piceid or 5 g RES. Oral administration of RES did not show an impact on total antioxidant capacity, ROS or CD. However, enzymatic activities of ROS scavenging SOD and CAT were significantly lower after high-dose compared to low-dose administration of RES (P<.03 and P<.01). In conclusion, in healthy subjects, neither 0.05 g nor 5 g RES changed blood oxidative state, although our in vitro data point to a prooxidative activity of low concentrations of RES and its metabolites, which could be important in vivo for individuals with compromised antioxidant defense capacity.