Radicals damage from

The same approach was used to study the reductive modification of a methionine residue (Met ) in the amyloid-/ peptide [A/ (l-40)] and its reversed sequence [A/ (40-l)]. The A/3 peptide suffers the highly selective attack of H atoms on the Met residue, with the formation of a modified peptide containing an a-amino-butyric acid residue. Formation of tw -lipids in POPC system as a marker of radical damage to A/3 peptide clearly shows the transfer of radical damage from the peptide to the lipid domain. 

Rachitic rosaiy, 582 RAC protein, 905 Radicals damage from ascorbic acid and, 626 vitamin E, 631,632 forrnation, 829... 

In concentration terms, thiols are the dominant cellular antioxidant the main biological thiol, the cysteinyl tripeptide, glutathione (GSH) has typical intracellular concentrations of a few millimolar [1]. The S-H bond strength is weaker than many C-H bonds, and hence free radical damage from cellular oxidative stress or radiation characterized by C-H bond breakage is potentially repairable by hydrogen donation [2, 3] ... 

Antioxidant Activity. Ascorbic acid serves as an antioxidant to protect intraceUular and extraceUular components from free-radical damage. It... 

Ascorbic acid—vitamin C—is an essential nutrient that the human body cannot manufacture from other compounds. It is needed for the formation of collagen, the protein that makes up connective tissue, and is essential to muscles, bones, cartilage, and blood vessels. It is a strong antioxidant, preventing damage from oxygen free radicals. 

These extensive alterations in cell structure and the biochemical machinery are indicative of entry into an ametabolic condition. In this condition damage from free radicals is potentially decreased, certainly the loss of chlorophyll and chloroplast structure removes a major source of free radical generation. About 50% of the extremely desiccation tolerant monocots exhibit extensive loss of chlorophyll and ultrastructural organisation when desiccated. Dicots, ferns and bryophytes retain most of their chlorophyll and exhibit small changes in structure when dry (see Gaff,... 

SASPs comprise about 10-20% of the protein in the dormant spore, exist in two forms alfi and y) d are degraded during germination. They are essential for expression of spore resistance to ultraviolet radiation and also appear to be involved in resistance to some biocides, e.g. hydrogen peroxide. Spores (a /3 ) deficient in a//3-type SASPs are much more peroxide-sensitive than are wild-type (normal) spores. It has been proposed that in wild-type spores DNA is saturated with a/j3-type SASPs and is thus protected from free radical damage. 

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). 

GSHPx, CAT and SOD, which normally protect cells from free-radical damage have not been detected in aqueous humour. It has therefore been su ested that damage by free radicals and hydrogen peroxide to the anterior segment is prevented by a non-enzymatic extracellular oxidoreduction system involving a constant supply of reduced glutathione to the aqueous fluid from the ciliary epithelium, cornea and lens (Riley, 1983). 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

It has been shown in many studies that protective effects of carotenoids can be observed only at small carotenoid concentrations, whereas at high concentrations carotenoids exert pro-oxidant effects via propagation of free radical damage (Chucair et al., 2007 Lowe et al., 1999 Palozza, 1998, 2001 Young and Lowe, 2001). For example, supplementation of rat retinal photoreceptors with small concentrations of lutein and zeaxanthin reduces apoptosis in photoreceptors, preserves mitochondrial potential, and prevents cytochrome c release from mitochondria subjected to oxidative stress induced by paraquat or hydrogen peroxide (Chucair et al., 2007). However, this protective effect has been observed only at low concentrations of xanthophylls, of 0.14 and 0.17 pM for lutein and zeaxanthin, respectively. Higher concentrations of carotenoids have led to deleterious effects (Chucair et al., 2007). 

In addition to the well-known iron effects on peroxidative processes, there are also other mechanisms of iron-initiated free radical damage, one of them, the effect of iron ions on calcium metabolism. It has been shown that an increase in free cytosolic calcium may affect cellular redox balance. Stoyanovsky and Cederbaum [174] showed that in the presence of NADPH or ascorbic acid iron ions induced calcium release from liver microsomes. Calcium release occurred only under aerobic conditions and was inhibited by antioxidants Trolox C, glutathione, and ascorbate. It was suggested that the activation of calcium releasing channels by the redox cycling of iron ions may be an important factor in the stimulation of various hepatic disorders in humans with iron overload. 

Overproduction of free radicals by erythrocytes and leukocytes and iron overload result in a sharp increase in free radical damage in T1 patients. Thus, Livrea et al. [385] found a twofold increase in the levels of conjugated dienes, MDA, and protein carbonyls with respect to control in serum from 42 (3-thalassemic patients. Simultaneously, there was a decrease in the content of antioxidant vitamins C (44%) and E (42%). It was suggested that the iron-induced liver damage in thalassemia may play a major role in the depletion of antioxidant vitamins. Plasma thiobarbituric acid-reactive substances (TBARS) and conjugated dienes were elevated in (3-thalassemic children compared to controls together with compensatory increase in SOD activity [386]. The development of lipid peroxidation in thalassemic erythrocytes probably depends on a decrease in reduced glutathione level and decreased catalase activity [387]. 

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. 

How does UV-induced free radical formation activate immune suppression Some have suggested that UV-induced cytokine production is involved. Because both DNA damage and oxidative stress can activate transcription of the cytokines that activate immune suppression,23>24one of the problems faced by investigators in the field was to divorce the effects of DNA damage from membrane oxidation. One approach was to look at the activation of transcription factors in UV-irradiated enucleated cells. Devary and colleagues25 observed that both NF-kB and AP-1 were activated in enucleated... 

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