ALPHA-TOCOPHERYL HYDROQUINONE IS AN EFFICIENT MULTIFUNCTIONAL INHIBITOR OF RADICAL-INITIATED OXIDATION OF LOW-DENSITY-LIPOPROTEIN LIPIDS

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 alpha-tocopheryl hydr oquinone (alpha-TQH(2)) strongly inhibited or completely prevented the (per)oxidation of ubiquinol-10 (CoQ(10)H(2)), alpha-tocopherol (alpha -TOH), and both surface and core lipids in LDL exposed to either aqueo us or lipophilic peroxyl radicals, Cu2+, soybean lipoxygenase, or the transition metal-containing Ham's F-10 medium in the absence or presen ce of human monocyte-derived macrophages. The antioxidant activity of alpha-TQH(2) was superior to that of several other lipophilic hydroqui nones, including endogenous CoQ(10)H(2), which is regarded as LDL's fi rst line of antioxidant defence, At least three independent activities contributed to the antioxidant action of alpha-TQH(2). First, alpha-T QH(2) readily associated with LDL and instantaneously reduced the lipo protein's ubiquinone-10 to CoQ(10)H(2), thereby maintaining this antio xidant in its active form. Second, alpha-TQH(2) directly intercepted a queous peroxyl radicals, as indicated by the increased rate of its con sumption with increasing rates of radical production, independent of L DL's content of CoQ(10)H(2) and alpha-TOH. Third, alpha-TQH(2) rapidly quenched alpha-tocopheroxyl radical in oxidizing LDL, as demonstrated directly by electron paramagnetic resonance spectroscopy. Similar ant ioxidant activities were also seen when alpha-TQH(2) was added to high -density lipoprotein or the protein-free Intralipid, indicating that t he potent antioxidant activity of alpha-TQH(2) was neither lipoprotein specific nor dependent on proteins. These results suggest that alpha- TQH(2) is a candidate for a therapeutic lipid-soluble antioxidant, As alpha-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 alpha-TQH(2) could be a previously unrecognized natural antioxid ant.