CONTRIBUTION OF VITAMIN-A TO THE OXIDATION RESISTANCE OF HUMAN LOW-DENSITY LIPOPROTEINS

This study investigated the antioxidant contribution of vitamin A in p rotecting human low density lipoprotein (LDL) against copper-stimulate d oxidation. The presence of small amounts of retinol (0.033 +/- 0.012 nmol/mol LDL) and retinyl palmitate (0.036 +/- 0.021 nmol/mol LDL) wa s routinely ascertained in the LDL. A single oral supplementation with 20,000 IU vitamin A caused a two- to three-fold increase of retinol a nd retinyl palmitate in the LDL isolated 8 h after the supplementation . In comparison to autologous-control LDL, vitamin A-enriched LDL were more resistant to oxidation, as expressed both by a clear delay in th e onset of lipid peroxidation and by a reduction of the rate of conjug ated diene hydroperoxide production during the propagation phase. The calculated incremental increase in the lag phase produced by 1 mol ret inol per mol LDL is about 1000 min, suggesting that retinol is more po tent than alpha-tocopherol in LDL. Oxidation experiments carried out w ith LDL isolated from plasma incubated in vitro with either retinol or retinyl palmitate indicated that retinol does lengthen the lag phase, whereas retinyl palmitate can slow the rate of peroxyl chain propagat ion, without affecting the duration of the lag phase. Temporal disappe arance of retinol and retinyl palmitate, followed in comparison with t hat of alpha-tocopherol and beta-carotene, indicated that the reactivi ty of the antioxidants with lipoperoxyl radicals was in the sequence a lpha-tocopherol, retinol, beta-carotene, and retinyl esters. Although the detailed antioxidant mechanism remains to be elucidated, these res ults suggest that LDL-associated vitamin A can play a role in maintain ing the antioxidant status of LDL during oxidative stress in vivo.