Free radical-mediated tissue damage

All extracts and their fractions showed HjOj-scavenging ciqiacity in a concentration-dependentmaimer. The values were lower for lOOppmasconqiared to those for 200 ppm level of extracts. The scavei ing of HjOj by extracts and their fractions is attributed to dieir phenolics udiich could donate electrons to HjOj, thus neutralizing it to water. The efficacy of the fractions of each extract was dependent on die chemical nature of phenolic conqiounds involved. Hius, crude extracts, their fractions or purified conqxHinds thereof may be incorporated into foods to minimize free radical-mediated l id peroxidation. They may also be used as alternative drugs/supplements to treat human diseases associated with free radical-mediated tissue damage. 

In summary, therefore, the evidence seems convincing that exercise modifies circulating and tissue concentrations of antioxidants and enzyme activities. It is much less certain that the fatigue or damage to skeletal muscle associated with various forms of excessive or unaccustomed exercise is initiated by free radical-mediated degradation. Considerably more work is required in this area to clarify the underlying pathogenic mechanisms. 

The brain has a number of characteristics that make it especially susceptible to free- radical-mediated injury. Brain lipids are highly enriched in polyunsaturated fatty acids and many regions of the brain, for example, the substantia nigra and the striatum, have high concentrations of iron. Both these factors increase the susceptibility of brain cell membranes to lipid peroxidation. Because the brain is critically dependent on aerobic metabolism, mitochondrial respiratory activity is higher than in many other tissues, increasing the risk of free radical Teak from mitochondria conversely, free radical damage to mitochondria in brain may be tolerated relatively poorly because of this dependence on aerobic metabolism. 

As noted earlier, peroxynitrite is formed with a diffusion-controlled rate from superoxide and nitric oxide (Reaction 10). As both these radicals are ubiquitous species, which present practically in all cells and tissues, peroxynitrite can be the most important species responsible for free radical-mediated damage in biological systems. Moreover, it is now known that NO synthases are capable of producing superoxide and nitric oxide simultaneously (see Chapter 22), greatly increasing the possible rate of peroxynitrite production. In addition, another enzyme xanthine dehydrogenase is also able to produce peroxynitrite in the presence of nitrite... 

Lipid peroxidation is one of the major sources of free-radical mediated injury that directly damages membranes and generates a number of secondary products. In particular, markers of lipid peroxidation have been found to be elevated in brain tissues and body fluids in several neurodegenerative diseases, and the role of lipid peroxidation has been extensively discussed in the context of their pathogenesis. Peroxidation of membrane lipids can have numerous effects, including increased membrane rigidity, decreased activity of membrane-bound enzymes (e.g., sodium pumps), altered activity of membrane receptors, and altered permeability [Anzai et al., 1999 Yehuda et al., 2002], In addition to effects on phospholipids, lipid-initiated radicals can also directly attack membrane proteins and induce lipid-lipid, lipid-protein, and protein-protein cross-linking, all of which obviously have effects on membrane function. 

Oxygenated acylglycerols. Lipid peroxidation in biological tissues attracts much attention because of its possible contribution to the functional modulation of biomembranes and lipoproteins. It is believed to be involved in free-radical-mediated damage, carcinogenesis and ageing processes. Research requires specific, sensitive and reproducible procedures to quantify the lipid hydroperoxides in each lipid class as primary products and the alcohols and aldehydes as secondary products of the peroxidation reaction. The identification and quantification of lipid oxidation products is therefore of great practical and theoretical interest and MS has assumed a major role in these analyses as a result of the development of mild ionization techniques. 

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