Linked Life Data

10232829

Source:http://linkedlifedata.com/resource/pubmed/id/10232829

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pubmed-article:10232829pubmed:abstractTextThe oxidative modification of low density lipoprotein (LDL) is thought to be an important factor in the initiation and development of atherosclerosis. Antioxidants have been shown to protect LDL from oxidation and to inhibit atherosclerosis development in animals. Potent synthetic antioxidants are currently being tested, but they are not necessarily safe for human use. We here characterize the antioxidant activity of IRFI005, the active metabolite of Raxofelast (IRFI0016) that is a novel synthetic analog of vitamin E under clinical development, and demonstrate that it prevents oxidative modification of LDL. IFI005 inhibited the oxidative modification of LDL, measured through the generation of MDA, electrophoretic mobility and apo B100 fluorescence. During the oxidation process IRF1005 was consumed with the formation of the benzoquinone oxidation product. The powerful antioxidant activity of IRFI005 is at least in part mediated by a chain breaking mechanism as it is an efficient peroxyl radical scavenger with a rate constant k(IRFI005 + LOO(o)) of 1.8 X 10(6) M(-1)s(-1). 4. IRFI005 substantially preserved LDL-associated antioxidants, alpha-tocopherol and carotenoids, and when co-incubated with physiologic levels of ascorbate provoked a synergistic inhibition of LDL oxidation. Also the co-incubation of IRFI005 with Trolox caused a synergistic effect, and a lag phase in the formation of the trolox-benzoquinone oxidation product. A synergistic inhibition of lipid peroxidation was also demonstrated by co-incubating IRFI005 and alpha-tocopherol incorporated in linoleic acid micelles. These data strongly suggest that IRFI005 can operate by a recycling mechanism similar to the vitamin E/ascorbate sysem.lld:pubmed
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pubmed-article:10232829pubmed:authorpubmed-author:VioliFFlld:pubmed
pubmed-article:10232829pubmed:authorpubmed-author:PedersenJ ZJZlld:pubmed
pubmed-article:10232829pubmed:authorpubmed-author:IulianoLLlld:pubmed
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pubmed-article:10232829pubmed:dateRevised2004-11-17lld:pubmed
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pubmed-article:10232829pubmed:year1999lld:pubmed
pubmed-article:10232829pubmed:articleTitleProtection of low density lipoprotein oxidation by the antioxidant agent IRFI005, a new synthetic hydrophilic vitamin E analogue.lld:pubmed
pubmed-article:10232829pubmed:affiliationInstitute of Clinical Medicine I, University La Sapienza, Rome, Italy. iuliano@uniroma1.itlld:pubmed
pubmed-article:10232829pubmed:publicationTypeJournal Articlelld:pubmed