Free radical-mediated chain oxidation of low density lipoprotein and its synergistic inhibition by vitamin E and vitamin C

The oxidation of human low density lipoprotein (LDL) initiated by free radical initiator and its inhibition by vitamin E and water-soluble antioxidants have been studied. It was found that the kinetic chain length was considerably larger than 1, suggesting that LDL was oxidized by a free radical chain mechanism. Vitamin E acted as a lipophilic chain-breaking antioxidant. Water-soluble chain-breaking antioxidants such as ascorbic acid and uric acid suppressed the oxidation of LDL initiated by aqueous radicals but they could not scavenge lipophilic radicals within LDL to break the chain propagation. Ascorbic acid acted as a synergistic antioxidant in conjunction with vitamin E.     

The location and function of vitamin E in membranes (review)

Vitamin E is a fat-soluble vitamin that consists of a group of tocols and tocotrienols with hydrophobic character, but possessing a hydroxyl substituent that confers an amphipathic character on them. The isomers of biological importance are the tocopherols, of which alpha-tocopherol is the most potent vitamin. Vitamin E partitions into lipoproteins and cell membranes, where it represents a minor constituent of most membranes. It has a major function in its action as a lipid antioxidant to protect the polyunsaturated membrane lipids against free radical attack. Other functions are believed to be to act as membrane stabilizers by forming complexes with the products of membrane lipid hydrolysis, such as lysophospholipids and free fatty acids. The main experimental approach to explain the functions of vitamin E in membranes has been to study its effects on the structure and stability of model phospholipid membranes. This review describes the function of vitamin E in membranes and reviews the current state of knowledge of the effect of vitamin E on the structure and phase behaviour of phospholipid model membranes.     

Ocular ascorbate transport and metabolism.

1. The concept is reviewed that the eye is subject to photo-oxidative damage through chemical free radical species that interact with sensitive tissue components. 2. The role of ascorbic acid may be to protect the eye by scavenging free radicals. 3. Ascorbic acid is present at a high concentration in various ocular compartments of diurnal animals, regardless of whether the animal synthesizes the compound or extracts it from the diet. 4. Ascorbic acid accumulates in the eye by active transport through the iris-ciliary body into aqueous humor, and subsequent transport into the lens and cornea. 5. Conservation of ascorbic acid occurs by reduction of dehydro-L-ascorbic acid and the ascorbate free radical through processes that appear to be enzymatic.     

Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microglia

Ascorbic acid (vitamin C) has been suggested to protect cerebral tissue in a variety of pathophysiological situations such as head trauma, ischemia or Alzheimer's disease. Most of these protective actions have been attributed to the antioxidative capacity of ascorbic acid. Besides the presence of elevated levels of oxygen radicals, prostaglandins produced by neurones and microglial cells seem to play an important role in prolonged tissue damage. We investigated whether ascorbic acid alone inhibits prostaglandin E2 (PGE2) synthesis and may augment the inhibitory effect of acetylsalicylic acid on prostaglandin synthesis. Ascorbic acid dose-dependently inhibited PGE2 synthesis in lipopolysaccharide-treated primary rat microglial cells (IC50 = 3.70 micro m). In combination with acetylsalicylic acid (IC50 = 1.85 micro m), ascorbic acid augmented the inhibitory effect of acetylsalicylic acid on PGE2 synthesis (IC50 = 0.25 micro m in combination with 100 micro m ascorbic acid). Ascorbic acid alone or in combination with acetylsalicylic acid did not inhibit cyclooxygenase-2 (COX-2) protein synthesis but inhibited COX-2 enzyme activity. Our results show that ascorbic acid and acetylsalicylic acid act synergistically in inhibiting PGE2 synthesis, which may help to explain a possible protective effect of ascorbic acid in various brain diseases.     

Antioxidant synergism of green tea polyphenols with alpha-tocopherol and L-ascorbic acid in SDS micelles

The synergistic antioxidant effect of polyphenols extracted from green tea, i.e. (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG) and gallic acid (GA), with alpha-tocopherol (vitamin E) and l-ascorbic acid (vitamin C) against the peroxidation of linoleic acid has been studied in sodium dodecyl sulfate (SDS) micelles. The peroxidation was initiated thermally by a water-soluble azo initiator 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH), and the reaction kinetics were studied by monitoring the formation of linoleic acid hydroperoxides and consumption of the antioxidants. It was found that the mixture of the green tea polyphenol, vitamin E and vitamin C could act synergistically to protect lipid peroxidation. Kinetic and mechanistic studies on the antioxidation process revealed that this antioxidant synergism was due to the regeneration of vitamin E by the green tea polyphenol and the regeneration of the latter by vitamin C.     

Vitamin E in aging, dementia, and Alzheimer's disease

Since its discovery, vitamin E has been extensively researched by a large number of investigators in an attempt to fully understand its role in a variety of pathophysiological contexts. The vast majority of published work has focused on vitamin E's antioxidant properties, which is why it is well known as a lipophilic antioxidant that protects membranes from being oxidatively damaged by free radicals. However, several lines of investigation have recently revealed that vitamin E has biological roles unrelated to its antioxidant properties. Among these roles, vitamin E has been described as: a regulator of signal transduction, gene expression, and redox sensor. In parallel with the discovery of novels cellular functions of vitamin E, the introduction of the free radical theory of brain aging has propelled a renewed interest in this vitamin. Most of the resulting work has been based on the postulate that, by preventing and/or minimizing the oxidative stress-dependent brain damage, vitamin E could be used as therapeutic approach. In this article, we will consider the existing literature regarding the biological properties of vitamin E and the potential therapeutic and/or preventative roles that this natural dietary factor plays in brain aging, cognition, and Alzheimer's dementia.     

Topical antioxidant vitamins C and E prevent UVB-radiation-induced peroxidation of eicosapentaenoic acid in pig skin

Eicosapentaenoic acid protects against UV-radiation-induced immunosuppression and photocarcinogenesis, but it is also prone to oxidative degradation, which may reduce or abolish its beneficial effects. The protective effect of topically applied vitamin E, vitamin C, or both against UVB-radiation-induced lipid peroxidation in the presence of eicosapentaenoic acid was investigated using an ex vivo pig skin model. Changes in the bioavailability of both antioxidants induced by UV radiation were studied in different skin compartments. The UVB-radiation dose used (25 kJ/m2) was similar to that required to induce immunosuppression in BALB/c mice. Exposure of pig skin with an epidermal eicosapentaenoic acid content of 1.0 +/- 0.3 mol% to UVB radiation resulted in an 85% increase of epidermal lipid peroxidation (P < 0.005). Topical application of vitamin E or vitamin C 60 min prior to UVB irradiation resulted in a major increase in both antioxidants in the stratum corneum and viable epidermis (P < 0.05). Vitamin E and vitamin C completely protected against UVB-radiation-induced lipid peroxidation (P < 0.005), but compared to vitamin E, a 500-fold higher vitamin C dose was needed. UVB irradiation induced a vitamin E consumption of up to 100% in the stratum corneum and viable epidermis, and a vitamin C consumption of only 21% in the stratum corneum. Simultaneously applied vitamin E and vitamin C also completely protected against UVB-radiation-induced lipid peroxidation (P < 0.05), and lower antioxidant doses were needed compared to vitamin E or vitamin C alone. In the presence of vitamin C, epidermal vitamin E was more stable upon UVB irradiation (P < 0.05), suggesting interaction between vitamin E and vitamin C. In conclusion, topically applied vitamin E and/or vitamin C efficiently protect against UVB-radiation-induced lipid peroxidation in the presence of eicosapentaenoic acid. The beneficial biological effects of eicosapentaenoic acid may therefore be improved if vitamin E and/or vitamin C are present in sufficient amounts. The ex vivo pig skin model provides a useful tool for assessing short-term biochemical effects related to UVB radiation, without the use of living experimental animals.     

Background level of 8-oxo-2'-deoxyguanosine in lymphocyte DNA does not correlate with the concentration of antioxidant vitamins in blood plasma.

Antioxidant vitamins, being effective free radical scavengers, can protect cellular DNA from oxidative damage. Therefore, in the present study we report on the relationship between basal level of 8-oxo-2'-deoxyguanosine in human lymphocyte DNA and the concentration of antioxidant vitamins (A, C and E). The average level of 8-oxo-2'-deoxyguanosine in lymphocytes of the studied group (15 males and 20 females) was 9.57 per 10(6) dG molecules. The endogenous level of ascorbic acid (vitamin C) in the plasma was, on average, 56.78 microM, while the mean concentrations of retinol (vitamin A) and alpha-tocopherol (vitamin E) were 1.24 uM and 25.74,uM, respectively. No correlations were found between individual 8-oxo-2 micro-deoxyguanosine levels in lymphocyte DNA and endogenous concentration of the vitamins.     

Significance of melatonin in antioxidative defense system: reactions and products

Melatonin is a potent endogenous free radical scavenger, actions that are independent of its many receptor-mediated effects. In the last several years, hundreds of publications have confirmed that melatonin is a broad-spectrum antioxidant. Melatonin has been reported to scavenge hydrogen peroxide (H(2)O(2)), hydroxyl radical (HO(.)), nitric oxide (NO(.)), peroxynitrite anion (ONOO(-)), hypochlorous acid (HOCl), singlet oxygen ((1)O(2)), superoxide anion (O(2)(-).) and peroxyl radical (LOO(.)), although the validity of its ability to scavenge O(2)(-). and LOO(.) is debatable. Regardless of the radicals scavenged, melatonin prevents oxidative damage at the level of cells, tissues, organs and organisms. The antioxidative mechanisms of melatonin seem different from classical antioxidants such as vitamin C, vitamin E and glutathione. As electron donors, classical antioxidants undergo redox cycling; thus, they have the potential to promote oxidation as well as prevent it. Melatonin, as an electron-rich molecule, may interact with free radicals via an additive reaction to form several stable end-products which are excreted in the urine. Melatonin does not undergo redox cycling and, thus, does not promote oxidation as shown under a variety of experimental conditions. From this point of view, melatonin can be considered a suicidal or terminal antioxidant which distinguishes it from the opportunistic antioxidants. Interestingly, the ability of melatonin to scavenge free radicals is not in a ratio of mole to mole. Indeed, one melatonin molecule scavenges two HO. Also, its secondary and tertiary metabolites, for example, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine, N-acetyl-5-methoxykynuramine and 6-hydroxymelatonin, which are believed to be generated when melatonin interacts with free radicals, are also regarded as effective free radical scavengers. The continuous free radical scavenging potential of the original molecule (melatonin) and its metabolites may be defined as a scavenging cascade reaction. Melatonin also synergizes with vitamin C, vitamin E and glutathione in the scavenging of free radicals. Melatonin has been detected in vegetables, fruits and a variety of herbs. In some plants, especially in flowers and seeds (the reproductive organs which are most vulnerable to oxidative insults), melatonin concentrations are several orders of magnitude higher than measured in the blood of vertebrates. Melatonin in plants not only provides an alternative exogenous source of melatonin for herbivores but also suggests that melatonin may be an important antioxidant in plants which protects them from a hostile environment that includes extreme heat, cold and pollution, all of which generate free radicals.     

Gastroprotective and Anti-oxidative Properties of Ascorbic Acid on Indomethacin-induced Gastric Injuries in Rats

Reactive oxygen species (ROS) have been implicated in the etiology of indomethacin-induced gastric mucosal damage. This study investigated ascorbic acid (vitamin C)'s protective effects against oxidative gastric mucosal damage induced by indomethacin. Ascorbic acid is a powerful antioxidant because it can donate a hydrogen atom and form a relatively stable ascorbyl free radical. We have investigated alterations in the levels of myeloperoxidase, antioxidant system enzymes (glutathione S-transferase, superoxide dismutase, glutathione reductase, catalase, glutathione peroxidase), lipid peroxidation and glutathione, as markers for ulceration process following oral administration of ascorbic acid, famotidine, lansoprazole, and ranitidine in rats with indomethacin-induced ulcers. In the present study, we found that (1) ascorbic acid, famotidine, lansoprazole and ranitidine reduced the development of indomethacin-induced gastric damages; (2) the administration of indomethacin caused a significant decrease in the levels of superoxide dismutase, glutathione peroxidase, glutathione S-transferase and glutathione, and an increase in the lipid peroxidation level; (3) the administration of ascorbic acid reversed the trend, inducing a significant increase of these enzymes' levels and a reduction in lipid peroxidation level in tissues; and (4) catalase, glutathione reductase and myeloperoxidase activities, increased by indomethacin, were found to be lower in the ascorbic acid, famotidine, lansoprazole and ranitidine-treated groups. The results indicate that the gastroprotective properties of ascorbic acid could be related to its positive effects on the antioxidant system and myeloperoxidase activity in indomethacin-induced gastric ulcers in rats.