Protective Effects of Antioxidants

The most extensive evidence that supports a role for free radicals in pathological conditions of the brain is provided by studies on experimental models of cerebral ischaemia/reperfusion. Although a burst of free-radical production occurs during the reperfusion phase after temporary cerebral ischaemia, the contribution of this radical burst to brain cell death can not be directly quantified. Perhaps the best way to quantify the contribution of free radicals to brain damage after ischaemia/ reperfusion is to assess damage after treatment with free-radical scavengers or antioxidants. Numerous studies have been reported where free-radical scavengers/ antioxidants have been used to try to ameliorate brain 

Free radicals are produced in the brain during the course of normal metabolism and are known to be involved in 

Andorn, A.C., Britton, R.S. and Bacon, B.R. (1990). Evidence that lipid peroxidation and total iron are increased in Alzheimer s brain. Neurobiol. Aging 11, 316-320. 

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Kim, H.S. and Lee, B.M., Protective effects of antioxidant supplementation on plasma lipid peroxidation in smokers, J. Toxicol. Environ. Health A, 63, 583, 2001. Gaziano, J.M. et al.. Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation. Atherosclerosis, 112, 187, 1995. Sutherland, W.H.F. et al.. Supplementation with tomato juice increases plasma lycopene but does not alter susceptibility to oxidation of low-density lipoproteins from renal transplant recipients, Clin. Nephrol, 52, 30, 1999. 

At the present time it is difficult to single out any one factor that could be held ultimately responsible for cell death after cerebral ischaemia. Recent studies, however, have provided us with sufficient evidence to conclude that free radical damage is at least one component in a chain of events that leads to cell death in ischaemia/reperfiision injury. As noted earlier in this review, much of the evidence for free radicals in the brain and the sources of free radicals come from studies in animals subjected to cerebral ischaemia. Perhaps the best evidence for a role for free radicals or reactive oxygen species in cerebral ischaemia is derived from studies that demonstrate protective effects of antioxidants. Antioxidants and inhibitors of lipid peroxidation have been shown to have profound protective effects in models of cerebral ischaemia. Details of some of these studies will be mentioned later. Several reviews have been written on the role of oxygen radicals in cerebral ischaemia (Braughler and HaU, 1989 Hall and Btaughler, 1989 Kontos, 1989 Floyd, 1990 Nelson ef /., 1992 Panetta and Clemens, 1993). 

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Bagchi D, Hassoun EA, Bagchi M, et al. 1993c. Protective effects of antioxidants against endrin-induced hepatic lipid peroxidation, DNA damage, and excretion of urinary lipid metabolites. Free Radical Biology Medicine 15 217-222. 

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Their role in oxidized-mediated cell death is also assessed (i) by the protective effect of antioxidants which reduce or inhibit oxidized LDL-induced ROS generation, caspase activation and subsequent apoptosis. 

Figure 2-19 Effect of Copper Concentration on Protective Effect of Antioxidants in Lard. (A) lard + 0.01% BHT, (B) lard + 0.01% ascorbyl palmitate, (C) lard + 0.005% BHT and 0.05% ascorbyl palmi-tate. Source From J. Pokorny, Stabilization of Fats by Phenolic Antioxidants, Can. Inst. Food Sci. Technol. J., Vol. 4, pp. 68—74, 1971.

Paromov, V., Kumari, S., Brannon, M., Myenyi, C., Stone, W.L. (2008). The protective effect of antioxidant liposomes in a human epidermal model exposed to a vesicating agent. Proceedings of the U.S. Army Medical Defense Bioscience Review, Hunt Valley, MD, 25 pp. 

In summary, oxysterols are known to exist in atherosclerotic lesions and have been demonstrated in cell-culture experiments to have profound cellular effects that could influence the development, progression, and reversal of atherosclerosis. The key question in this field of research, however, is whether the concentrations of oxysterols in vivo are high enough to influence atherogenesis. Thus far, only the oxysterol-activated nuclear transcription pathway has been directly supported by in vivo data, and even in this case the precise roles and identification of the activating oxysterols in vivo have not yet been elucidated. Moreover, to the extent that oxysterols are generated in vivo and not just obtained from the diet, their role in human atherosclerosis has been questioned by clinical trials showing little or no protective effect of antioxidants on atherosclerotic coronary artery disease (K.J. Williams and E.A. Fisher, 2005). 

Ranks, D.. and Soliman, M. R. (1997). Protective effects of antioxidants against benomyl-induced lipid peroxidation and glutathione depletion in rats. Toxicology IS, 177-181. 

Negre-Salvayre A, Alomar Y, Troly M, Salvayre R. Ultraviolet-treated lipoproteins as a model sy stem for the study of the biological effects of lipid peroxides on cultured cells. III. The protective effect of antioxidants (probucol, catechin, vitamin E) against the cytotoxicity of oxidized LDL occurs in two different ways. Biochim Biophy Acta 1991 1096 291-300. 

Bagchi, M. et al.. Protective effects of antioxidants against smokeless tobacco-induced oxidative stress and modulation of Bcl-2 and p53 genes in human oral keratinocytes. Free Radical Res., 35, 181,2001. 

Milatovic, D., Gupta, R.C., Yu, Y, et al., 2011c. Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury. Toxicol. Appl. Pharmacol. 256, 219-226. 

Dihydroquercetin (taxifolin, DHQ) is a natural flavonoid, which possesses antioxidant activity and other pharmacological properties (anti-inflammatory, anti-atherosclerotic, etc.). Dihydroquercetin is hydrophobic compound, that s why it can t be administered intravenously, also its oral bioavailability is reduced. Recently, many new dihydroquercetin derivatives were synthesized, including water-soluble forms (cyclodextrin inclusion complexes with dihydroquercetin derivatives). In addition to the protective effect of antioxidants against lipid peroxidation, increasing attention is paid to the possibilities of antioxidants including dihydroquercetin to prevent an oxidation of proteins. Fibrinogen is more susceptible to oxidation than most other plasma proteins. 

In addition to the protective effect of antioxidants against damage to cell membranes increasing attention is paid to the possibilities of antioxidants to prevent oxidation of proteins. It is generally reeognized today that many amino acid residues of proteins are susceptible to oxidation by reactive oxygen species (ROS). Free-radical oxidation of proteins may be accompanied by the splitting of the pol q)eptide chains, a modifica-... 

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