Susceptibility of human LDL to oxidative modification. Effects of variations in beta-carotene concentration and oxygen tension.
Epidemiological studies suggest that beta-carotene supplementation may decrease atherosclerotic events. Because beta-carotene is transported in low-density lipoprotein (LDL), one mechanism by which this protective effect may occur is through direct inhibition of LDL oxidation. Addition of beta-carotene to LDL in vitro inhibits the susceptibility of LDL to oxidation. In contrast, we have shown that feeding large doses of beta-carotene results in beta-carotene-enriched plasma LDL (16- to 35-fold), but such LDL does not show increased resistance to oxidation. Potential criticisms of our initial study relate to the unique antioxidant properties of beta-carotene. Beta-Carotene provides better quenching of some free radicals, such as singlet oxygen, than others. Additionally, since beta-carotene can easily autooxidize, forming metabolites that can also generate free radicals, it has been argued that at sufficient concentrations in vivo the antioxidant effect of beta-carotene may be diminished. It has thus been suggested that in our initial study we may have failed to properly assess the unique antioxidant effects of beta-carotene by our selection of oxidizing conditions and/or failed to achieve antioxidant activity because of excessive enrichment of LDL with beta-carotene. We now report the effects of feeding lower doses of beta-carotene on the susceptibility of LDL to oxidation and test whether any antioxidant activity of beta-carotene can be detected when different modes of initiating oxidation are used. Because the antioxidant activity of beta-carotene is reputedly most pronounced in low-oxygen environments, we also investigated its effect on LDL oxidation under conditions of reduced oxygen tension.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Endocrinology and Metabolism, University of California, San Diego 92093-0682.
P D
PD
Reaven
E
E
Ferguson
M
M
Navab
F L
FL
Powell
D000328:Adult; D002338:Carotenoids / Q000008:administration & dosage / Q000494:pharmacology*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D019207:beta Carotene
D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D019207:beta Carotene; D002338:Carotenoids; D010100:Oxygen