Resveratrol, a phytoalexin (3, 4', 5, trihydroxystilbene) present in some red wines,
has been reported to inhibit copper-mediated low-density lipoprotein (LDL) oxidation.
In this study, we examined the efficiency of this compound in inhibiting metal ion-dependent
and independent peroxidation of porcine LDL. At 0.5, 1, or 1.5 microM, transresveratrol
prolonged the lag time preceding the onset of conjugated diene formation in a dose-dependent
manner, with a slope of the propagation phase 5-fold greater in the presence of Cu
SO4 (5 microM) than in the presence of the free radical generator, AAPH [2, 2'-azobis
(2-amidinopropane) dihydrochloride] (1 mM). At 1 microM, transresveratrol prolonged
the lag time 3.4- and 1.4-fold in the presence of copper and AAPH, respectively. Isomerisation
into cisresveratrol significantly lowered the chelating capacity, but did not alter
the free radical scavenging capacity. As compared to flavonoids and trolox, transresveratrol
showed a much higher ability to prolong the lag time in copper, but not in AAPH-catalyzed
oxidation. The kinetics of generation of degradative products in the presence of copper
confirmed the strongest protective effects of transresveratrol, because the formation
of thiobarbituric acid reactive substances and hydroperoxides was almost completely
inhibited at 200 min. By contrast, transresveratrol was less potent than flavonoids
(but more than trolox) as a scavenger of free radicals. Our data show that, like flavonoids,
resveratrol protects LDL against peroxidative degradation by both chelating and free
radical scavenging mechanisms. However, transresveratrol, which is by far the most
potent chelator of copper, does not chelate iron. It might contribute to the protective
effects of wine polyphenols by removing copper from LDL particles and arterial tissue
and, thereby, delaying the consumption of flavonoids and endogenous antioxidants.