Antioxidants against free-radical damage

Ascorbate has multiple antioxidant capacities and may be the most important water-soluble defence against free-radical damage in human plasma. At millimolar concentrations, ascorbate scavenges O2, OH and HOCl (Blake et al., 1983). The latter reaction protects plasma lipids against degradation by activated PMNs. 

Although it is common believe that phenolic compounds like vitamin E exert a protective role against free radical damage, antioxidant molecules can exert additional biological functions. The estrogen 17-P-estradiol, for instance, has antioxidant capacity [3] which has been proposed to protect women from coronary artery disease, but the determination of secondary sexual features is not mediated by its antioxidant activity. All-trans-retino is again a potent antioxidant [4], but the main function of retinol in rhodopsin and vision is not related with this property. 

Antioxidants derived from foods help to protect against free radical damage. Carotenoids are a very important class of antioxidants, as are vitamins A, C, and E. Carotenoids, including alpha carotene, beta carotene, lycopene, lutein, and zexanthin, have been demonstrated to protect against skin cancer, prostate cancer, and atherosclerosis, among others. Higher blood antioxidant levels have been correlated with lower blood levels of C-reactive protein (CRP), and thus lower inflammation of the blood vessels (and less atherosclerotic plaque). 

The most important lipophilic antioxidant that acts in eucary-otic cells to protect unsaturated lipids against free radical damage is vitamin E, especially a-tocopherol. Along with P-carotene and coenzyme Q, it protects the structure and integrity of biomembranes, such as the cytoplasmic cell membrane (or plasmolema) and intracellular membranes of organelles (nucleus, mitochondria, lysosome and endoplasmic reticulum). It k ako employed in the protection of lipoproteins present in plasma. It is transported in the bloodstream by association with the lipid phase of low density Hpoprotein (LDL) particles (see Section 3.6.1). Each LDL particle contains six molecules of vitamin E. 

Contemporary interest in ubiquinones is explained by their potential antioxidant activity and the possibility of using these nontoxic natural compounds as pharmaceutical agents. But it should be noted that ubiquinones are not vitamins and that they are synthesized in humans. Taking into account a high level of ubiquinones in mitochondria, the effective supplementation of ubiquinones to fight against free radical-mediated damage seems to be a hard task. 

In 1986, the antioxidant effects of thioredoxin reductase were studied by Schallreuter et al. [81]. It has been shown that thioredoxin reductase was contained in the plasma membrane surface of human keratinocytes where it provided skin protection against free radical mediated damage. Later on, the reductive activity of Trx/thioredoxin reductase system has been shown for the reduction of ascorbyl radical to ascorbate [82], the redox regulation of NFkB factor [83], and in the regulation of nitric oxide-nitric oxide synthase activities [84,85],... 

Qian, Z. J., Jung, W. K., Byun, H. G., and Kim, S. K. (2008b). Protective effect of an antioxidative peptide purified from gastrointestinal digests of oyster, Crassostrea gigas against free radical induced DNA damage. Bioresour. Technol. 99,3365-3371. 

Many antioxidants quoted as potential protective agents against free-radical-induced DNA damage have more than one phenolic group. Their chemistry is, therefore, also of some interest in the present context. The semiquinone radicals, derived from hydroquinone by one-electron oxidation or from 1,4-benzoqui-none by one-electron reduction, are in equilibrium with their parents (Roginsky et al. 1999), and these equilibria play a role in the autoxidation of hydroquinone (Eyer 1991 Roginsky and Barsukova 2000). Superoxide radials are intermediates in these reactions. 

Free radical damage is considered to be a causative factor in the development of cancer and inflammatory and chronic diseases. Therefore, free radical scavenging molecules (antioxidants) may play a beneficial role in these conditions. With repect to CVD, the oxidation of low-density lipoprotein (LDL) is believed to be a critical process in the development of atherosclerosis (Berliner et al., 1995 Navab et al., 1995). The presence of oxidized LDL in the intima of an artery leads to the production of macrophage-derived foam cells, the main cell type present in fatty streaks that are believed to be the earliest lesion of atherosclerosis (Fuster, 1994). Therefore, the use of antioxidants as dietary supplements to protect against LDL oxidation may reduce both the development and progression of atherosclerosis (Gey, 1995). 

It was observed that people with low carotenoid intake or low blood levels have an increased risk of degenerative diseases. In a number of these diseases free radical damage plays a role in the pathophysiology of the disease. Earlier studies were focused mainly on p-carotene and the lycopene protective effect against prostate and lung cancer, but there is as yet no definitive proof for a causal relationship or for a beneficial antioxidant effect of carotenoids. 

The cited works demonstrated that oleuropein and hydroxy-tyrosol are potent antioxidants against lipid peroxidation in phospholipid bilayers, induced by aqueous oxygen radicals. These results may be very interesting, because biphenols could have important applications in human diseases caused by free radical damage. 

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