Lipid-soluble antioxidant

In fact, we found that a-tocopherol, an antioxidant lipid-soluble vitamin, prevented geranylgeranoic acid-induced apoptotic cell death of human hepatoma cells. These results are presented in Figure 1 (Shidoji et al 1997). 

Vitamin E is the Major Lipid-Soluble Antioxidant in Cell Membranes Plasma Lipoproteins... 

Natural antioxidants may be classified according to their nutritive value or according to their solubility. The hydrophobic vitamin E and the hydrophilic vitamin C are thus important both as nutrients and as antioxidants. The nonnutritive antioxidants may similarly be divided into lipid-soluble and water-soluble antioxidants, as shown in Fig. 16.3, which will also form the basis for a discussion of exploitation of combinations of anhoxidants in order to improve protective effects. 

The solubility of antioxidants determines their phase distribution in foods. It has been observed that compared to lipid-soluble antioxidants water-soluble antioxidants like ascorbate yield better protection to strongly lipophilic food systems like pure oils. In contrast, antioxidants soluble in lipids like the tocopherols yield better protection to oil-in-water emulsions when compared to water-soluble antioxidants (Porter, 1993). The explanation offered for this... 

Tesoriere, L. et ah. Biothiols, taurine, and lipid-soluble antioxidants in the edible pulp of Sicilian cactus pear (Opuntia ficus-indica) fruits and changes of bioactive juice components upon industrial processing, J. Agric. Food Chem., 53, 7851, 2005. 

The food technologist may be especially interested in the fate of the carotenoids in the seed oil. Like red palm oil, the resulting carotenoid-pigmented canola oil may be more stable due to the antioxidant properties of carotenoids and may be more attractive to consumers. Alternatively, for food security concerns, transgenic soybean or canola oils and seed meals that are genetically modified for more efficient bio-diesel production may be bio-safety marked with lipid-soluble carotenoids and water-soluble anthocyanins, respectively. Potatoes are excellent potential sources of dietary carotenoids, and over-expression of CrtB in tubers led to the accumulation of P-carotene. Potatoes normally have low levels of leaf-type carotenoids, like canola cotyledons. 

The time-scale of this haem conversion is related to the antioxidant status of the LDL and that of the erythrocyte lysate. The incorporation of lipid-soluble antioxidants, such as tocopherol and butylated hydroxy-toluene (BHT) at specific time points during the LDL-erythrocyte interaction, prolongs the lag phase to oxidation, eliminates the oxy to ferryl conversion of the haemoglobin and delays the oxidative modification of the LDL. 

Burton, G., Joyce, A. and Ingold, K.U. (1983). Is vitamin E the only lipid-soluble, chain-breaking antioxidant in human blood plasma and erythrocyte membranes Arch. Biochem. Biophys. 221, 281-290. 

The major lipid-soluble antioxidant primarily associated with lipid membranes is a-tocopherol (vitamin E). Circulating a-tocopherol is carried by chylomicrons, LDL and HDL and also has extracellular antioxidant capacities. As a chain-breaking antioxidant, it short circuits the propagation phase of lipid peroxidation because the peroxyl radical will react with a-tocopherol more rapidly than a polyunsaturated ffitty acid (Burton and Traber, 1990). The resulting a-tocopheryl radical reacts with a second peroxyl radical to form an inactive, nonradical complex. In vitro, ascorbate regenerates the tocopheryl radical into its native non-radical form (Burton and Traber, 1990). 

The importance of vitamin E for maintenance of lipid integrity in vivo is emphasized by the fact that it is the only major lipid-soluble chain-breaking antioxidant found within plasma, red cells and tissue cells. Esterbauer etal. (1991) have shown that the oxidation resistance of LDL increases proportionately with a-tocopherol concentration. In patients with RA, synovial fluid concentrations of a-tocopherol are significantly lower relative to paired serum samples (Fairburn et al., 1992). The low level of vitamin E within the inflamed joint implies it is being consumed via its role in terminating lipid peroxidation and this will be discussed further in Section 3.3. 

Esterbauer et al. (1991) have demonstrated that /3-carotene becomes an effective antioxidant after the depletion of vitamin E. Our studies of LDL isolated from matched rheumatoid serum and synovial fluid demonstrate a depletion of /8-carotene (Section 2.2.2.2). Oncley et al. (1952) stated that the progressive changes in the absorption spectra of LDL were correlated with the autooxidation of constituent fatty acids, the auto-oxidation being the most likely cause of carotenoid degradation. The observation that /3-carotene levels in synovial fluid LDL are lower than those of matched plasma LDL (Section 2.2.2) is interesting in that /3-carotene functions as the most effective antioxidant under conditions of low fOi (Burton and Traber, 1990). As discussed above (Section 2.1.3), the rheumatoid joint is both hypoxic and acidotic. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples (Fairburn etal., 1992). This difference could not be accounted for by the lower concentrations of lipids and lipoproteins within synovial fluid. The low levels of both vitamin E and /3-carotene in rheumatoid synovial fluid are consistent with the consumption of lipid-soluble antioxidants within the arthritic joint due to their role in terminating the process of lipid peroxidation (Fairburn et al., 1992). 

The effect of prolonged antioxidant therapy in relation to normal physiological processes (for example, redox cycling, cell-cell signalling, transcription factor activation) must be assessed. It is conceivable that the overload of one antioxidant by dietary supplementation (for example, a-tocopherol) may shift the levels of other antioxidants (for example, by decreasing ascorbate and /3-carotene concentrations), with unknown consequences. To assess the potential for lipid-soluble antioxidant treatment in inflammatory diseases such as RA, further investigations into these questions will be needed. 

Hiramatsu, M., Edamatsu, R., Ohyama, H. and Mori, A. (1992). Effect of Japanese herbal medicine, sho-saiko-to-go-keishi-kashakuyaku-to (TJ-960) on aging. In Lipid-soluble Antioxidants Biochemistry and Clinical Applications (eds. A.S.H. Ong and L. Packer) pp. 535-552. Birkhauser Verlag, Basel. 

Phenols are important antioxidants, with vitamin E being the most important endogenous phenolic membrane-bound antioxidant. Membrane levels of vitamin E are maintained through recycling of the vitamin E radical with ascorbate and thiol reductants. Vitamin E is a mixture of four lipid-soluble tocopherols, a-tocopherol being the most efiective radical quencher. The reaction of a-tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate was recently reported. These are facile reactions that result in mixed dimer adducts (Yamauchi etal., 1993). 

Fullerene Cgo also functions efficiently as an antioxidant, actually being better than other lipid-soluble antioxidants at scavenging reactive oxygen species (ROS) (Wang et al., 1999). Water-soluble derivatives of C o, such as a poly-hydroxyl form, are able to function in the same respect in aqueous environments. 

Ju Z and WJ Bramlage. 1999. Phenolics and lipid-soluble antioxidants in fruit cuticle of apples and their antioxidant activities in model systems. Postharv Biol Technol 16 107—118. 

The photochemiluminiscence (PCL) assay was initially used by Popov and others (1987). Popov and Lewin (1994 1996) have extensively studied this technique to determine water-soluble and lipid-soluble antioxidants. The PCL assay measures the antioxidant capacity, toward the 02 radical, in lipidic and water phase. This method allows the quantification of both the antioxidant capacity of hydrophilic and/or lipophilic substances, either as pure compounds or complex matrices from different origin synthetic, vegetable, animal, human, etc. The PCL method is based on an approximately 1,000-fold acceleration of the oxidative reactions in vitro by the presence of an appropriate photosensitizer. The PCL is a very quick and sensitive method. Chua and others (2008) used this assay to determine the antioxidant potential of Cin-namomum osmophloeum, whereas Kaneh and Wang and others (2006) determined the antioxidant capacity of marigold flowers. The antioxidant activity of tree nut oil extracts was also assessed by this method (Miraliakbari and Shahidi 2008). 

Popov IN and Lewin G. 1996. Photochemiluminescent detection of antiradical activity. IV. Testing of lipid-soluble antioxidants. J Biochem Biophys Methods 31(1-2) 1-8. 

Figure 7 shows an example of the measurements of the antioxidant capacity of lipid-soluble compounds (ACL). In this figure, recording 1 corresponds to blank, while recordings 2-5 demonstrate the effect of adding lipid extracts from equivalently 20,40, 60, and 80 pL of blood plasma from a healthy volunteer... 

Figure 10 Lipid-soluble antioxidants in blood plasma in rabbits fed 4 weeks with probu-col and two newly synthesized compounds. All products were administered in equal amounts. The VE portion is the dark gray portion of the columns. Contr., control group Prob., group fed with probucol S-1 and S-2, groups fed with new antioxidants.

In 1988 Bast and Haenen [201] reported that both LA and DHLA did not affect iron-stimulated microsomal lipid peroxidation. However, Scholich et al. [202] found that DHLA inhibited NADPH-stimulated microsomal lipid peroxidation in the presence of iron-ADP complex. Inhibitory effect was observed only in the presence of a-tocopherol, suggesting that some interaction takes place between these two antioxidants. Stimulatory and inhibitory effects of DHLA have also been shown in other transition metal-stimulated lipid peroxidation systems [203,204]. Later on, the ability of DHLA (but not LA) to react with water-soluble and lipid-soluble peroxyl radicals has been proven [205], But it is possible that the double (stimulatory and inhibitory) effect of DHLA on lipid peroxidation originates from subsequent reactions of the DHLA free radical, capable of participating in new initiating processes. 

Ubiquinones (coenzymes Q) Q9 and Qi0 are essential cofactors (electron carriers) in the mitochondrial electron transport chain. They play a key role shuttling electrons from NADH and succinate dehydrogenases to the cytochrome b-c1 complex in the inner mitochondrial membrane. Ubiquinones are lipid-soluble compounds containing a redox active quinoid ring and a tail of 50 (Qio) or 45 (Q9) carbon atoms (Figure 29.10). The predominant ubiquinone in humans is Qio while in rodents it is Q9. Ubiquinones are especially abundant in the mitochondrial respiratory chain where their concentration is about 100 times higher than that of other electron carriers. Ubihydroquinone Q10 is also found in LDL where it supposedly exhibits the antioxidant activity (see Chapter 23). 

Vitamin E (tocopherol), which is a major lipid-soluble antioxidant, inhibits the differentiation of smooth muscle presumably by modulating the activity of protein kinase C. PKC inhibition by tocopherol has also been implied in human platelets. 

Tocopherols are the second major class of lipid-soluble antioxidants inphotosynthetic membranes. Their primary function is to protect cells from hpid peroxidation. The water-soluble ascorbic acid also significantly acts against hpid peroxidation and DNA damage. However, these low-molecular weight antioxidants are chemically consumed and hence not considered the most efficient detoxifying agents. 

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