NO - Besoin d'assistance

Mechanisms and Biomarkers (WG 4) page 55
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and Frei (1995). All together these results do not suggest significant protection. Consequently,
the protective effects of β-carotene against cardiovascular disease are most likely not
mediated by increased protection of LDL against oxidation in the arterial wall. Alternative
mechanisms, such as the reduced capacity of arterial wall cells to modify LDL, preservation
of endothelial vasodilator function, and increased serum HDL levels, have been suggested
(Hatta and Frei, 1995).
Vitamin C - Ascorbate is not carried within the LDL particle because of its high
hydrophilicity, consequently there are other possible ways in which it may reduce LDL
oxidative susceptibility (Frei et al., 1996): 1) by reducing preformed lipid hydroperoxides and
preventing propagation of lipid peroxidation in LDL; 2) by scavenging of radicals and
oxidants in the aqueous phase; 3) by regenerating the endogenous antioxidants (α-tocopherol,
β-carotene) from oxidation; 4) by modification of histidine residues and other copper-binding
sites on apo B (by dehydroascorbate or another oxidation product). Ascorbate has been shown
to protect LDL from oxidation in vitro (Jialal and Grundy, 1991; Frei B, 1991; Frei et al.,
1996), however results obtained by in vivo studies are conflicting and difficult to compare due
to differences in the experimental protocol. Fuller et al. (1996) and Wen et al. (1997)
performed a similar study supplementing smokers with 1000 mg ascorbic acid for 4 weeks
and studying the resistance of LDL to copper induced oxidation compared to a control group.
Fuller et al. (1996) found that the ascorbate-supplemented group had a significant reduction in
LDL oxidative susceptibility as measured by thiobarbituric acid-reactive substances (TBARS)
and the formation of conjugated dienes; Wen et al. (1997) found no effect on the lag phase of
conjugated diene production or TBARS formation to copper induced oxidation, while plasma
lipid peroxides measured as malondialdehyde were reduced significantly in the vitamin C
supplemented group. This could be explained considering that a relatively large amount of
free radicals could be scavenged by high plasma ascorbate concentrations, confirming that
vitamin C is more effective in the aqueous phase. However, in the Fuller et al., study subjects
followed a low ascorbate diet for 2 weeks before supplementation and this could have
modified the baseline values of LDL oxidizability.
Short-term supplementation with vitamin C (1 - 1.5 g/day) for 2 weeks showed a protective
effect on in vivo oxidation of LDL after smoking as measured by the content of TBARS in
isolated LDL (Harats et al., 1990). Furthermore an increase in the lag period of LDL
oxidation was evidenced (Harats et al., 1998) after a dietary enrichment with citrus fruit