Original ContributionsComparative study on dynamics of antioxidative action of α-tocopheryl hydroquinone, ubiquinol, and α-tocopherol against lipid peroxidation
Introduction
With increasing evidence that shows the involvement of active oxygen species and free radicals in a variety of diseases, cancer, and aging, the beneficial effects of antioxidants have received much attention. The aerobic organisms are protected from such oxidative stress by a variety of antioxidants with different functions. To scavenge active free radicals is one of the important functions of antioxidants, and vitamins E and C are well known as most abundant and potent lipophilic and hydrophilic radical scavenging antioxidants, respectively. TQH2, a reduced form of TQ, which is one of the metabolites of TOH, has been shown to be capable of acting as a radical-scavenging antioxidant.
It has been observed that TQ exists with its reduced form TQH2 in animal tissues including liver, heart, spleen, adipose, and brain [1], [2], [3], [4], [5], [6] and in human tissues [7], [8], [9], [10]. TQ can be reduced to TQH2 in rat liver microsomal, mitochondrial, cytosolic preparations, and isolated hepatocytes [2], [11], [12], and it has been shown that TQ is converted into TQH2 in humans [7]. Moreover, cytochrome P450 reductase and quinone oxidoreductase were found to catalyze TQH2 formation from TQ in cell-free and cellular systems [13]. The role of TQ and TQH2 as antioxidants has received attention. Bindoli reported that TQH2 was a much more potent antioxidant than TQ in inhibiting lipid peroxidation induced by ascorbate/Fe(II) in liposomes and by cumene hydroperoxide in submitochondrial particles [11]. TQ was found to be a more effective antioxidant than TOH in a tissue culture system whenever they were concurrently added or preadded [14]. TQ-pretreated cells were more resistant to lipid peroxidation and cytotoxicity than control cells [15], [16], [17], [18]. The antioxidant activity of TQ in these studies has so far been suggested, presumably because of the production of TQH2, and TQ itself is not considered to be an effective antioxidant [19]. Recently, it has also been reported that TQH2 prevented cumene hydroperoxide-induced lipid peroxidation in rat liver microsomes [13], and it strongly inhibited the oxidation of both surface and core lipids in low-density lipoprotein (LDL) [20].
Ubiquinol (UQH2), a reduced form of coenzyme Q (UQ), has been shown to act as a radical scavenging antioxidant in solution [21], [22], [23], [24], liposomes [24], [25], [26], mitochondria [27], [28], [29], [30], [31], microsomes [21], [28], [29], LDL [23], [32], [33], cell [34], and in whole animal [35], [36].
The antioxidant nature of TQH2, however, has not been studied as extensively as UQH2 and TOH. Moreover, the dynamics and efficacy of ubiquinol as an antioxidant have not been well elucidated either. The present study was carried out, therefore, to investigate and elucidate the inherent activities of TQH2, UQH2, and TOH as radical-scavenging antioxidants and also the interactions between these antioxidants. The basic information is necessary for understanding the antioxidant action in a biologic system.
The reactivity toward radicals and antioxidant activity of TQH2 were assessed and compared to UQH2 and TOH as follows. First, we measured the reactivity and the stoichiometric numbers of the three substances for the reactions with galvinoxyl, a stable phenoxyl radical. Second, their ability to scavenge peroxyl radicals derived from AMVN was studied in various solvents. Third, the oxidation of methyl linoleate induced by AMVN where lipid peroxyl radical is a predominant chain carrier was used to test their ability to inhibit lipid oxidation in organic solution and in aqueous micelle emulsions. Furthermore, parallel experiments were carried out to trace their consumptions in the various reaction systems. Finally, the ability of TQH2 and UQH2 to reduce α-tocopheroxyl radical was investigated in various solvents.
Section snippets
Reagents
The materials, TQ, galvinoxyl, and AMVN, were purchased from Wako Pure Chemical Co. Ltd. (Osaka, Japan). Methyl linoleate was obtained from Sigma Chemical Co. (St. Louis, MO, USA) and purified before use by column chromatography as described previously [37]. DPPD and 2-methyl-6-phenyl-3,7-dihydroimidazo [1,2-a]pyrazin-3-one(CLA), a cyprodina luciferin analog, used as a chemiluminescence probe were obtained from Tokyo Kasei Co. (Tokyo, Japan). TOH, UQ, and 2,2,5,7,8-pentamethyl-6-chromanol (PMC)
Kinetic and stoichiometric studies on the reaction of TQH2, UQH2, and TOH with galvinoxyl
To estimate quantitatively the reactivities toward oxygen radicals, the reactions of TQH2, UQH2, and TOH with galvinoxyl were measured by following a decrease in absorption at 428 nm with a stopped-flow spectrophotometer (Fig. 2A) and the pseudo first-order rate constant k1 was calculated [38]. The results in Fig. 2B show that the pseudo first-order rate constant k1 values obtained for each antioxidant were linearly dependent on their concentrations. The slope of the plots yielded the
Discussion
Our results clearly show that TQH2 possesses higher reactivity toward galvinoxyl and peroxyl radical than does either UQH2 or TOH. The rate constants for the reaction of TQH2, UQH2, and TOH with galvinoxyl obtained in this study at 25°C in ethanol are comparable with those determined by Mukai et al. [50] toward similar, but not identical, hindered phenoxyl radical under similar conditions. The stoichiometric numbers obtained for the reaction with galvinoxyl (Table 1) prove that both TQH2 and UQH
Acknowledgements
We thank Dr. Mareyuki Takahashi’s kind help. This study was supported in part by Grant-in-Aid for Scientific Research and COE Research from the Ministry of Education, Science, Sports and Culture, Japan, and Research for the Future Program by the Japan Society for the Promotion of Science.
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