Effects of antioxidants on the oxidative susceptibility of low-density lipoprotein.
An important event in the pathogenesis of atherosclerosis is believed to be the oxidative modification of low-density lipoprotein (LDL) initiated by a free radical-driven lipid peroxidation process. Vitamin E acts as a lipophilic chain-breaking antioxidant, while water-soluble chain-breaking antioxidants such as vitamin C or uric acid suppress the oxidation of LDL initiated by aqueous radicals. In this study, we established a new method of measuring the lag time of inhibited lipid peroxidation using the lipophilic azo radical initiator V-70:2-2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) and investigated in vitro the susceptibility of LDL to oxidation using this method when lipid- and water-soluble antioxidants were added. When the lipid-soluble antioxidant, vitamin E, was added to LDL, the lag time was extended whereas a higher dose of vitamin E led to a shortened lag time of V-70-induced lipid peroxidation in LDL. These results suggest that vitamin E radicals (tocopheroxyl radicals) act as prooxidants during the autoxidation of LDL. It was also shown that the shortened lag time induced by higher doses of vitamin E was restored when lipid- and water-soluble antioxidants were added simultaneously, which suggests that vitamin E radicals derived from vitamin E are subsequently reduced by vitamin C to regenerate vitamin E. Thus, the interaction between lipid- and water-soluble antioxidants provides an important function in maintaining LDL resistance to oxidation.
Hirano
R
R
Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo, Japan.
Kondo
K
K
Iwamoto
T
T
Igarashi
O
O
Itakura
H
H
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001391:Azo Compounds / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D011341:Probucol / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001391:Azo Compounds; D008077:Lipoproteins, LDL; D009570:Nitriles; D016877:Oxidants; D014810:Vitamin E; C109522:V 70; D014527:Uric Acid; D011341:Probucol; D001205:Ascorbic Acid