Review ArticleRole of vitamin E as a lipid-soluble peroxyl radical scavenger: in vitro and in vivo evidence
Graphical abstract
Introduction
The aerobic organisms are protected from oxidative stress induced by reactive oxygen/nitrogen species (ROS/RNS)1 by an elaborate defense network in which multiple antioxidants with diverse functions play their roles [1], [2]. Some antioxidants are small molecules, whereas others are macromolecules such as proteins and enzymes. The physiological antioxidant systems have several lines of defense. In the first line, antioxidants prevent the production of ROS/RNS and other reactive species by, for example, sequestering active metal ions and reducing hydroperoxides and hydrogen peroxide to hydroxides and water, respectively. In the second defense line, antioxidants scavenge, quench, or remove ROS/RNS and other reactive species before they attack biological molecules. In the third defense line, antioxidant compounds and enzymes repair the damage and reconstitute membranes and tissues. Furthermore, low levels of oxidative stress induce an adaptive response, which accelerates the production of antioxidant proteins and enzymes and transfers them to the right site at the right time and in the right amounts [3], [4]. Thus, antioxidants act cooperatively and synergistically in the defense network to cope with oxidative stress. Oxidative stress proceeds by both free radical-mediated mechanisms and non-free radical mechanisms. Both free radical and nonradical oxidants attack and modify biological molecules, and the disruption of thiol redox circuits induced by, at least in part, ROS/RNS also causes oxidative stress [5].
Radical scavenging is one of the important functions of antioxidants. Several kinds of free radicals are involved in vivo, such as superoxide (O2•−), hydroxyl (HO•), alkoxyl (RO•), peroxyl (RO2•), aryloxyl (ArO•), nitric oxide (•NO), nitrogen dioxide (NO2•), thiyl (RS•), thiyl peroxyl (RSOO•), sulfonyl (RSO2OO•), and carbon-centered radicals (R•). Some radicals are quite reactive, whereas others are not. Superoxide and nitric oxide are not reactive enough per se to directly attack biological molecules. Free radicals attack biologically essential molecules such as lipids, proteins, carbohydrates, and DNA by hydrogen atom abstraction, addition to double bond, and electron transfer reactions. Similarly, free radical-scavenging antioxidants (IH) react with free radicals by one of the following three reaction mechanisms. The relative importance of these reactions depends on the radicals, antioxidants, and microenvironment:hydrogen abstraction, X•+IH→XH+I•;addition, X•+CC→XCC•;electron transfer, X•+IH→X−+IH•+→X−+I•+H+.
Vitamin E, vitamin C, carotenoids, ubiquinol (reduced form of coenzyme Q), uric acid, bilirubin, and thiyl compounds are major radical-scavenging antioxidants in vivo. Notably, vitamin E and vitamin C are the essential lipophilic and hydrophilic radical-scavenging antioxidants, respectively. It was suggested that vitamin E may also function as a signaling mediator independent of antioxidant function, which is a matter of debate [6], [7]. This article presents the evidence that vitamin E acts as a peroxyl radical-scavenging antioxidant in vitro and in vivo.
Section snippets
Mechanisms, dynamics, and efficacy of radical scavenging by vitamin E
Vitamin E has eight isoforms, α-, β-, γ-, and δ-tocopherol and α-, β-, γ-, and δ-tocotrienol [8]. Tocopherols have a saturated side chain, called a phytyl side chain, at the 2 position of the chromanol ring, whereas tocotrienols have a side chain with three double bonds at positions 3′, 7′, and 11′. α forms have three methyl groups on the chromanol head at positions 5, 7, and 8. There are two methyl groups on the chromanol head in the β (positions 5 and 8) and γ (positions 7 and 8) forms,
In vitro evidence of scavenging of peroxyl radicals by vitamin E
The action of vitamin E as an antioxidant against in vitro lipid peroxidation has been studied extensively [reviewed in 23,65]. The mechanisms and dynamics of lipid peroxidation have also been studied extensively and are now well understood [115], [116]. Numerous studies show clearly that vitamin E inhibits lipid peroxidation in the test tube as assessed by oxygen uptake, substrate consumption, and lipid peroxidation products formation. PUFAs are quite vulnerable to oxidation. Methyl linoleate
In vivo evidence of scavenging of peroxyl radicals by vitamin E
The action of vitamin E as a peroxyl radical-scavenging antioxidant in vivo may be assessed by the level and distribution of lipid peroxidation products measured in biological fluids and tissues as a marker. For this purpose, it is important to understand the mechanisms and products of lipid oxidation. Lipids are oxidized in vivo by multiple oxidants and mechanisms to give diverse products [128]. The major lipid oxidation products mediated by free radicals are hydroperoxides, which are reduced
Concluding remarks
Collectively, it may be stated that vitamin E, above all α-tocopherol, exerts antioxidant effects by scavenging lipid peroxyl radicals in in vivo as well as in vitro systems. It should be added that vitamin E is not an efficient scavenger of hydroxyl radical, alkoxyl radical, nitrogen dioxide, thiyl radical, ozone, hypochlorite, and probably singlet oxygen in vivo. It may be noted that the effects of antioxidant supplementation including vitamin E to well-nourished subjects are often small and
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