Multiple reactive oxygen/nitrogen species induce oxidative stress. Mammals have evolved with an elaborate defense network against oxidative stress, in which multiple antioxidant compounds and enzymes ...with different functions exert their respective roles. Radical scavenging is one of the essential roles of antioxidants and vitamin E is the most abundant and important lipophilic radical-scavenging antioxidant in vivo. The kinetic data and physiological molar ratio of vitamin E to substrates show that the peroxyl radicals are the only radicals that vitamin E can scavenge to break chain propagation efficiently and that vitamin E is unable to act as a potent scavenger of hydroxyl, alkoxyl, nitrogen dioxide, and thiyl radicals in vivo. The preventive effect of vitamin E against the oxidation mediated by nonradical oxidants such as hypochlorite, singlet oxygen, ozone, and enzymes may be limited in vivo. The synergistic interaction of vitamin E and vitamin C is effective for enhancing the antioxidant capacity of vitamin E. The in vitro and in vivo evidence of the function of vitamin E as a peroxyl radical-scavenging antioxidant and inhibitor of lipid peroxidation is presented.
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•Vitamin E is a lipophilic radical-scavenging antioxidant.•Vitamin E scavenges only peroxyl radicals efficiently in vivo.•Vitamin E is not an efficient scavenger of hydroxyl, alkoxyl, thiyl, or NO2 radicals.•Vitamin E inhibits lipid peroxidation by breaking chain propagation both in vitro and in vivo.
The role and beneficial effects of antioxidants against various disorders and diseases induced by oxidative stress have received much attention. Many types of antioxidants with different functions ...play their role in the defense network
in vivo. The free radical scavenging antioxidants are one of the important classes of antioxidants and the assessment of their capacity has been the subject of extensive studies and argument. Various methods have been developed and applied in different systems, but many available methods result in inconsistent results. There is no simple universal method by which antioxidant capacity can be assessed accurately and quantitatively. In this review article, the available methods are critically reviewed on the basis of the mechanisms and dynamics of antioxidant action, and the methods are proposed to assess the capacity of radical scavenging and inhibition of lipid peroxidation both
in vitro and
in vivo. It is emphasized that the prevailing competition methods such as oxygen radical absorption capacity (ORAC) using a reference probe may be useful for assessing the capacity for scavenging free radicals but that such methods do not evaluate the characteristics of antioxidants and do not necessarily show the capacity to suppress the oxidation, that is, antioxidation. It is recommended that the capacity of antioxidant compounds and their mixtures for antioxidation should be assessed from their effect on the levels of plasma lipid peroxidation
in vitro and biomarkers of oxidative stress
in vivo.
Lipid peroxidation (LPO) has been shown to induce disturbance of membrane organization and functional loss and modification of proteins and DNA bases, and it has been implicated in the pathogenesis ...of various diseases. At the same time, LPO products have been shown to act as redox signaling mediators. Free and ester forms of both polyunsaturated fatty acids and cholesterol are important substrates for LPO
in vivo and they are oxidized by both enzymatic and nonenzymatic mechanisms to give a variety of products. The results of numerous studies reported in the literatures show that the levels of LPO products in plasma of healthy human subjects are below 1 μM and that the molar ratios of LPO products to the respective parent lipids are below 1/1000, that is, below 0.1%. The levels of LPO products in human erythrocytes were found to be higher than those in plasma. Considerable levels of cholesterol oxidation products were observed. Although many LPO products exert cyctotoxicity, sublethal concentrations of LPO products induce cellular adaptive responses and enhance tolerance against subsequent oxidative stress through upregulation of antioxidant compounds and enzymes. This adaptive response is observed not only for chemically reactive α,β-unsaturated carbonyl compounds such as 4-hydroxy-2-nonenal and 15-deoxy-delta-12,14-prostaglandin J
2 but also for chemically stable compounds such as hydroxyoctadecadienoic acid, hydroxylcholesterol, and lysophosphatidylcholine. Such opposite dual functions of LPO products imply that LPO, and probably oxidative stress in general, may exert both deleterious and beneficial effects
in vivo. LPO as well as reactive oxygen and nitrogen species has been shown to play an important role as a regulator of gene expression and cellular signaling messenger. In order to exert physiologically important functions as a regulator of gene expression and mediator of cellular signaling, the formation of LPO products must be strictly controlled and programmed. In contrast to LPO products by enzymatic oxidation, it appears difficult to regulate the formation of free radical-mediated LPO products. Even such unregulated LPO products may exert beneficial effects at low levels, but excessive unregulated LPO may lead to pathological disorders and diseases.
Free radical-mediated lipid peroxidation has been implicated in a number of human diseases. Diverse methods have been developed and applied to measure lipid peroxidation products as potential ...biomarkers to assess oxidative stress status in vivo, discover early indication of disease, diagnose progression of disease, and evaluate the effectiveness of drugs and antioxidants for treatment of disease and maintenance of health, respectively. However, standardized methods are not yet established.
Characteristics of various lipid peroxidation products as biomarkers are reviewed on the basis of mechanisms and dynamics of their formation and metabolism and also on the methods of measurement, with an emphasis on the advantages and limitations.
Lipid hydroxides such as hydroxyoctadecadienoic acids (HODE), hydroxyeicosatetraenoic acids (HETE), and hydroxycholesterols may be recommended as reliable biomarkers. Notably, the four HODEs, 9-cis,trans, 9-trans,trans, 13-cis,trans, and 13-trans,trans-HODE, can be measured separately by LC–MS/MS and the trans,trans-forms are specific marker of free radical mediated lipid peroxidation. Further, isoprostanes and neuroprostanes are useful biomarker of lipid peroxidation. It is important to examine the distribution and temporal change of these biomarkers.
Despite the fact that lipid peroxidation products are non-specific biomarkers, they will enable to assess oxidative stress status, disease state, and effects of drugs and antioxidants. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.
•Reliable biomarkers are needed to assess oxidative stress status and disease state.•Lipid peroxidation is involved in pathogenesis of various diseases.•Advantages and limitations of lipid peroxidation products as biomarkers are discussed.•HODE, HETE, hydroxycholesterol, and isoprostane may be used as reliable biomarkers.•These biomarkers may be used for assessment of antioxidant capacity in vivo.
There is a growing consensus that reactive oxygen species (ROS) are not just associated with various pathologies, but that they act as physiological redox signaling messenger with important ...regulatory functions. It is sometimes stated that “if ROS is a physiological signaling messenger, then removal of ROS by antioxidants such as vitamins E and C may not be good for human health.” However, it should be noted that ROS acting as physiological signaling messenger and ROS removed by antioxidants are not the same. The lipid peroxidation products of polyunsaturated fatty acids and cholesterol induce adaptive response and enhance defense capacity against subsequent oxidative insults, but it is unlikely that these lipid peroxidation products are physiological signaling messenger produced on purpose. The removal of ROS and inhibition of lipid peroxidation by antioxidants should be beneficial for human health, although it has to be noted also that they may not be an effective inhibitor of oxidative damage mediated by non-radical oxidants. The term ROS is vague and, as there are many ROS and antioxidants which are different in chemistry, it is imperative to explicitly specify ROS and antioxidant to understand the effects and role of oxidative stress and antioxidants properly.
► Reactive oxygen/nitrogen species, ROS/RNS, have dual functions. ► Lipid oxidation products exert both harmful and beneficial effects. ► Lipid peroxidaton (LPO) products may induce adaptive ...response. ► Radical scavenging antioxidants do not impair physiological signaling. ► Inhibition of LPO by antioxidants should be beneficial for human health.
Oxidative modification of biologically essential molecules by reactive oxygen and nitrogen species (ROS/RNS) has been implicated in the pathogenesis of various diseases. At the same time, roles of ROS/RNS as physiological signaling messenger have been established. Lipid oxidation products also have two faces. It is argued that the radical scavenging antioxidants taken from diet or supplement may impair such beneficial effects of ROS/RNS and lipid oxidation products. However, it is unlikely that antioxidants impair physiologically important signaling, since the antioxidants do not scavenge signaling ROS/RNS nor do they inhibit the formation of signaling molecules. Lipid peroxidation products are not produced on purpose and inhibition of lipid peroxidation by antioxidants should be beneficial for maintenance of health and reducing disease risk.
Oxidative stress induced by reactive oxygen and nitrogen species has been implicated in the pathogenesis of various disorders and diseases. Biomarkers are needed for assessment of oxidative stress ...status in vivo and also for health examination, diagnosis at early stage, prognosis, safe and efficient drug development, and evaluation of efficacy of drugs, foods, beverages, and supplements. Lipids are susceptible to oxidation and lipid peroxidation products are potential biomarkers for oxidative stress status in vivo and its related diseases. Recently, isoprostane, isoprostaglandin homologues from arachidonic acid, neuroprostanes from docosahexaenoic acid, hydroxyoctadecadienoic acid from linoleic acid, and oxysterols from cholesterol have received much attention as potential biomarkers for oxidative stress status in vivo. The physiological levels of these lipid peroxidation products and potential application as biomarkers will be reviewed.
Oxidative stress and lipid peroxidation have been implicated in the pathogenesis of various diseases, including atherosclerosis and fatty liver diseases, and consequently the role of antioxidants in ...the prevention and treatment of such diseases has received much attention. In particular, the effects of vitamin E, the most important lipophilic radical-scavenging antioxidant, have been investigated extensively. Many in vitro, animal, and epidemiological studies have reported positive results, but large-scale randomized controlled intervention studies and meta-analyses have produced inconsistent and often disappointing results. In the present review article, the role and action of vitamin E are discussed, with consideration of the factors that determine the outcome of vitamin E treatment. Vitamin E should benefit subjects experiencing oxidative stress due to free radicals when administered at the correct time and for an appropriate duration.
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