Tocopherol antioxidant activity

Besides scavenging peroxyl radicals, tocopherols and tocotrienols are also excellent quenchers for singlet oxygen and peroxynitrile (39). It has been reported that ot-tocopherol shows a pro-oxidant activity when present at high concentrations (106-108). It was later found that tocopherols do not show a pro-oxidant effect if they are compared with controls devoid of them and other lipid-related antioxidants (109, 110). However, tocopherols lose their antioxidant efficacy at high concentrations because they participate in a number of reactions that lead to production of alkoxyl radicals that consume tocopherols and initiate new reaction chains because of their low selectivity (111, 112). Using a kinetic approach, a number of reactions were found to contribute to the loss of tocopherol antioxidant activity that is greater for a-tocopherol than for y-tocopherol (113). 

Vitamin E is the generic name for molecules with a-tocopherol antioxidant activity, including all tocopherol and tocotrienol derivatives [86], with a similar chromanol structure trimethyl (a-), dimethyl (P- or 7-), and monomethyl (8-) (Figure 6.17). 

Following the action of extraordinary stimulants (hypoxic hypoxia, hypoxia + hyperoxia, hypodynamia + hyperthermia), animals demonstrate an accumulation of malonic dialdehyde with a simultaneous fall of antiradical activity of the liver tissue. A preliminary introduction to rats of acetylene amine 3,4,5-tris(morpho-linopropynyl)-l-methylpyrazole 103 and also of tocopherol antioxidant and gutumine antihypoxant averts activation of the lipid peroxidation processes. The inhibition of peroxidation with this agent is mediated by stabilization of ly-zosomal and mitochondrial membranes. Unsaturated amines prevent destruction of the organelle membranes provoked by UV irradiation and incubation at 37°C (pH4.7)(78MIl). 

XU z, HUA N, GODBER s (2001) Antioxidant activity of tocopherols, tocotrienols, and y-oryzanol components from rice bran against cholesterol oxidation accelerated by 2, 2 -azobis(2-methylpropionamidine) dihydrochloride. J Agri Food Chem, 49 2077-81. 

It has been established that carotenoid structure has a great influence in its antioxidant activity for example, canthaxanthin and astaxanthin show better antioxidant activities than 3-carotene or zeaxanthin. 3- 3 3-Carotene also showed prooxidant activity in oil-in-water emulsions evaluated by the formation of lipid hydroperoxides, hexanal, or 2-heptenal the activity was reverted with a- and y-tocopherol. Carotenoid antioxidant activity against radicals has been established. In order of decreasing activity, the results are lycopene > 3-cryptoxanthin > lutein = zeaxanthin > a-carotene > echineone > canthaxanthin = astaxanthin. ... 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

Carvediol is a vasodilator with beta-adrenergic antagonist activity. It has cardioprotective activity in animal models. The antioxidant effect of carvediol was compared with five other beta blockers in iron-initiated lipid peroxidation, where it inhibited TBARs formation and protected membrane-bound tocopherol in rat brain homogenate (Yue et al., 1992a). The ortJ <)-substituted phenoxylethyl-amine is responsible for the improved antioxidant activity. 

As mentioned earlier, ascorbate and ubihydroquinone regenerate a-tocopherol contained in a LDL particle and by this may enhance its antioxidant activity. Stocker and his coworkers [123] suggest that this role of ubihydroquinone is especially important. However, it is questionable because ubihydroquinone content in LDL is very small and only 50% to 60% of LDL particles contain a molecule of ubihydroquinone. Moreover, there is another apparently much more effective co-antioxidant of a-tocopherol in LDL particles, namely, nitric oxide [125], It has been already mentioned that nitric oxide exhibits both antioxidant and prooxidant effects depending on the 02 /NO ratio [42]. It is important that NO concentrates up to 25-fold in lipid membranes and LDL compartments due to the high lipid partition coefficient, charge neutrality, and small molecular radius [126,127]. Because of this, the value of 02 /N0 ratio should be very small, and the antioxidant effect of NO must exceed the prooxidant effect of peroxynitrite. As the rate constants for the recombination reaction of NO with peroxyl radicals are close to diffusion limit (about 109 1 mol 1 s 1 [125]), NO will inhibit both Reactions (7) and (8) and by that spare a-tocopherol in LDL oxidation. 

Belkner et al. [32] demonstrated that 15-LOX oxidized preferably LDL cholesterol esters. Even in the presence of free linoleic acid, cholesteryl linoleate continued to be a major LOX substrate. It was also found that the depletion of LDL from a-tocopherol has not prevented the LDL oxidation. This is of a special interest in connection with the role of a-tocopherol in LDL oxidation. As the majority of cholesteryl esters is normally buried in the core of a lipoprotein particle and cannot be directly oxidized by LOX, it has been suggested that LDL oxidation might be initiated by a-tocopheryl radical formed during the oxidation of a-tocopherol [33,34]. Correspondingly, it was concluded that the oxidation of LDL by soybean and recombinant human 15-LOXs may occur by two pathways (a) LDL-free fatty acids are oxidized enzymatically with the formation of a-tocopheryl radical, and (b) the a-tocopheryl-mediated oxidation of cholesteryl esters occurs via a nonenzymatic way. Pro and con proofs related to the prooxidant role of a-tocopherol were considered in Chapter 25 in connection with the study of nonenzymatic lipid oxidation and in Chapter 29 dedicated to antioxidants. It should be stressed that comparison of the possible effects of a-tocopherol and nitric oxide on LDL oxidation does not support importance of a-tocopherol prooxidant activity. It should be mentioned that the above data describing the activity of cholesteryl esters in LDL oxidation are in contradiction with some earlier results. Thus in 1988, Sparrow et al. [35] suggested that the 15-LOX-catalyzed oxidation of LDL is accelerated in the presence of phospholipase A2, i.e., the hydrolysis of cholesterol esters is an important step in LDL oxidation. 

There are numerous other polyphenolic compounds possessing in vitro and in vivo antioxidative activity. Several examples of these compounds are cited below. One of nonflavonoid polyphenols of particular interest is resveratrol (3,5,4 -trihydroxy-Znmv-stilbcne, Figure 29.8), which has been identified as a potential cancer chemopreventive agent and an antimutagen [182]. It has been found that resveratrol is the efficient inhibitor of cyclooxygenase and the inhibitor of free radical-mediated cellular processes. For example, resveratrol is a better free radical scavenger than a-tocopherol or ascorbic acid but has nearly the same activity as... 

Another fat-soluble vitamin, E, was found by Evans and Bishop in 1923. Pregnant rats on a defined diet (alcohol-extracted casein, cornstarch, and lard) supplemented with butter (vitamins A and D) and yeast extract (vitamin B group) produced few young because of fetal resorption. Male rats on the same diet were sterile. The disorders, which have not been identified in man, were corrected by wheat-germ oil, from which tocopherol, the active ingredient, was isolated in 1936. In spite of intensive investigations and a recognition that the vitamin is an antioxidant and destroyer of free radicals, the function of vitamin E remains obscure. 

Cannabidiol and THC reduced neurotoxicty induced by glutamate in cortical neurons (Hampson et al. 1998). This result was effective for toxicity induced at both NMDA and AMPA/kainate receptors, and was independent of cannabinoid receptor activity. The mechanism of neuroprotection appears to be by their potent antioxidant activity. They were even more protective against glutamate neurotoxicity than either ascorbate or o-tocopherol. 

In 1989, Kato et al. reported the isolation of carazostatin (247) from Streptomyces chromofuscus. Carazostatin represents a novel radical scavenger more active than butylated hydroxytoluene (BHT) (226). Moreover, it exhibits strong inhibitory activity against the free radical-induced, lipid peroxidation in liposomal membranes, and shows stronger antioxidant activity than ot-tocopherol (227). 

Benzoxathiins, considered as 4-thiaflavans, have shown antimicrobial <2004MI317> and antioxidant activity and seem to operate by both the flavonoid-like and the tocopherol-like mechanisms <2001CC551, 20050BC3066>. 

Antioxidant activity was also tested in a liver microsome system. In this study, mice were treated by oral intubation (2 times/wk) with 0.2 ml olive oil alone or containing CLA (0.1 ml), linoleic acid (0.1 ml), or dl-a-tocopherol (lOmg). Four weeks after the first treatment, liver microsomes were prepared and subsequently subjected to oxidative stress using a non-enzymatic iron-dependent lipid peroxidation system. Microsomal lipid peroxidation was measured as thiobarbituric acid-reactive substance (TBARS) production using malondialdehyde as the standard. It was found that pretreatment of mice with CLA or dl-a-tocopherol significantly decreased TBARS formation in mouse liver microsomes (p < 0.05) (Sword, J. T. and M. W. Pariza, University of Wisconsin, unpublished data). 

At higher concentrations, the antioxidant activities of thymol and carvacrol were close to that of a-tocopherol and were in fact responsible for the antioxidant activity of many EOs which contain them [12, 17, 139, 153, 163, 164, 168, 170-174]. The high potential of phenolic components to scavenge radicals might be explained by their ability to donate a hydrogen atom from their phenolic hydroxyl groups [175]. 

Mallet, J. R, C. Cerrati, E. Ucciani, J. Gamisans, and M. Gruber. 1994. Antioxidant activity of plant leaves in relation to their alpha-tocopherol content. Food Chem. 49 61-65. 

As mentioned earlier, ascorbate and ubihydroquinone regenerate a-tocopherol contained in a LDL particle and by this may enhance its antioxidant activity. Stocker and his coworkers... 

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