Alpha-tocopheryl hydroquinone is an efficient multifunctional inhibitor of radical-initiated oxidation of low density lipoprotein lipids
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 94 (1997-07-22), Heft 15
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Zugriff:
As the oxidation of low density lipoprotein (LDL) lipids may be a key event in atherogenesis, there is interest in antioxidants as potential anti-atherogenic compounds. Here we report that α-tocopheryl hydroquinone (α-TQH 2 ) strongly inhibited or completely prevented the (per)oxidation of ubiquinol-10 (CoQ 10 H 2 ), α-tocopherol (α-TOH), and both surface and core lipids in LDL exposed to either aqueous or lipophilic peroxyl radicals, Cu 2+ , soybean lipoxygenase, or the transition metal-containing Ham’s F-10 medium in the absence or presence of human monocyte-derived macrophages. The antioxidant activity of α-TQH 2 was superior to that of several other lipophilic hydroquinones, including endogenous CoQ 10 H 2 , which is regarded as LDL’s first line of antioxidant defence. At least three independent activities contributed to the antioxidant action of α-TQH 2 . First, α-TQH 2 readily associated with LDL and instantaneously reduced the lipoprotein’s ubiquinone-10 to CoQ 10 H 2 , thereby maintaining this antioxidant in its active form. Second, α-TQH 2 directly intercepted aqueous peroxyl radicals, as indicated by the increased rate of its consumption with increasing rates of radical production, independent of LDL’s content of CoQ 10 H 2 and α-TOH. Third, α-TQH 2 rapidly quenched α-tocopheroxyl radical in oxidizing LDL, as demonstrated directly by electron paramagnetic resonance spectroscopy. Similar antioxidant activities were also seen when α-TQH 2 was added to high-density lipoprotein or the protein-free Intralipid, indicating that the potent antioxidant activity of α-TQH 2 was neither lipoprotein specific nor dependent on proteins. These results suggest that α-TQH 2 is a candidate for a therapeutic lipid-soluble antioxidant. As α-tocopherylquinone is formed in vivo at sites of oxidative stress, including human atherosclerotic plaque, and biological systems exist that reduce the quinone to the hydroquinone, our results also suggest that α-TQH 2 could be a previously unrecognized natural antioxidant.
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Alpha-tocopheryl hydroquinone is an efficient multifunctional inhibitor of radical-initiated oxidation of low density lipoprotein lipids
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Autor/in / Beteiligte Person: | Stocker, Roland ; Witting, Paul K. ; Neuzil, Jiri |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 94 (1997-07-22), Heft 15 |
Veröffentlichung: | 1997 |
Medientyp: | unknown |
ISSN: | 0027-8424 (print) |
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