Antioxidant defences

A recent review [5] concluded that there is little convincing evidence that vitamin E increases antioxidant defences in the body. This would also question a benefit of vitamin E in the prevention and management of the diseases mentioned above. 

WEI z, PENG Q and lau b h s (1997) Pycnogenol enhances endothelial cell antioxidant defences Redox Report 3, 147-55. 

Diabetic patients have reduced antioxidant defences and suffer from an increased risk of free radical-mediated diseases such as coronary heart disease. EC has a pronounced insulin-like effect on erythrocyte membrane-bound acetylcholinesterase in type II diabetic patients (Rizvi and Zaid, 2001). Tea polyphenols were shown to possess anti-diabetic activity and to be effective both in the prevention and treatment of diabetes (Choi et al, 1998 Yang et al, 1999). The main mechanism by which tea polyphenols appear to lower serum glucose levels is via the inhibition of the activity of the starch digesting enzyme, amylase. Tea inhibits both salivary and intestinal amylase, so that starch is broken down more slowly and the rise in serum glucose is thus reduced. In addition, tea may affect the intestinal absorption of glucose. 

Meat products have to be stabilised in some cases, as meat lipids contain no natural antioxidants or only traces of tocopherols. Most muscle foods contain, however, an efficient multi-component antioxidant defence system based on enzymes, but the balance changes adversely on storage. The denaturation of muscle proteins is the main cause of the inbalance as iron may be released from its complexes, catalysing the lipid oxidation. Salting contributes to the negative effects of storage, as it enhances oxidation. Using encapsulated salt eliminates the deleterious effect of sodium chloride. 

This research was part of the frame programme Antioxidative Defence Interaction between Nutritive and Non-nutritive Antioxidants sponsored by the F0TEK programme (Danish Research Councils) through LMC-Centre for Advanced Food Studies. 

Del Boccio, C., Laprenna, D., Porreca, E., Pennilli, A., Savini, F., Feliciani, P., Ricci, G. and CuccuruUo, F. (1990). Aortic antioxidant defence mechanisms time-related changes in cholesterol fed rabbits. Atherosclerosis 81, 127-135. 

Bilirubin (normal plasma concentration < 20 iM) is able to scavenge singlet oxygen and peroxyl radicals. It has been proposed that bilirubin bound to human albumin contributes significantly to the non-enzymic antioxidant defences in human plasma (Stocker and Ames, 1987). 

Frei, B., Stocker, R. and Ames, B.N. (1988). Antioxidant defences and lipid peroxidation in human blood plasma. Proc. Natl Acad. Sci. USA 85, 9748-9752. 

Stocker, R. and Frei, B. (1991). Endogenous antioxidant defences in human plasma. In Oxidative Stress, Oxidants and Antioxidants (ed. H. Sies) pp. 213-243, Academic Press, London. 

Human chronic inflammatory diseases are characterized by populations of cells with altered regulation and function. A large body of evidence suggests that many of these cellular abnormalities may be linked to an increase in the production of free radicals and/or deficiencies of antioxidant defence systems. Oxygen free radicals attack cell structures, altering their function, and are cytotoxic. They have therefore been implicated in the pathogenesis of rheumatoid arthritis as well as many other human diseases (HaUiwell, 1991). 

This chapter addresses (1) the mechanisms, antioxidant defences and consequences in relation to free-radical production in the inflamed rheumatoid joint (2) lipid abnormalities in RA (3) the potential contribution of ox-LDL to RA (the role of ox-LDL in coronary heart disease is discussed in Chapters 2 and 3 and will not be fully discussed here) and (4) the therapeutic aspects of chain-breaking antioxidant interventions in RA. 

Mechanisms, Antioxidant Defences and Consequences of Free-radical Production in the Rheumatoid Joint... 

The efficient removal of O2 and H2O2 vvill diminish OH formation and therefore antioxidant defence systems have evolved to limit their accumulation. Enzymic and low molecular weight antioxidants exist to scavenge free radicals as self-protection mechanisms. Some proteins exhibit antioxidant properties because they chelate transition-metal catalysts. The significance of antioxidants in relation to inflammatory joint disease is discussed below. 

Under normal physiological conditions, therefore, antioxidant defences in the skin are able to modulate free-radical production. The initiation of an inflammatory event has the potential for increasing ROS production to such an extent that defence systems are overwhelmed and tissue damage occurs. This event results in the production of even more toxic oxidants and the development of overt disease requiring treatment. Section 4 of this chapter will describe the role of ROS in skin inflammation. 

Moysan, A., Marquis, I., Gaboriau, F., Santus, R., Dubertret, L. and Morliere, P. (1993). Ultraviolet A-induced lipid peroxidation and antioxidant defence systems in cultured skin fibroblasts. J. Invest. Dermatol. 100, 692-698. 

Injury (either physical or chemical) to the comeal endothelial cells has a marked efiect on occular function as these cells are responsible for maintaining the thickness and clarity of the cornea, yet they cannot be replaced if damaged. Immunohistochemical studies have revealed that enzymatic antioxidant defences, SOD, CAT and GSHPx, are similarly distributed in the corneal epithelium and endothelium (Rao etal., 1985 Attala et d., 1987, 1988). Other antioxidants include ascorbate, carotenoids and vitamin E (Fleath, 1962). 

Guyan et al. 1990) have used several markers of lipid peroxidation (9-cis-, 11-tmns-isomer of linoleic acid, conjugated dienes and ultraviolet fluorescent products) to demonstrate significant increases in the duodenal aspirate after secretin stimulation in patients with acute and clinic pancreatitis. They interpreted this as indicating induction of hepatic and pancreatic drug-metabolizing enzymes in the face of a shortfidl of antioxidant defences, more marked in chronic pancreatitis. Subsequent studies in patients with chronic pancreatitis have confirmed decreased serum concentrations of selenium, -carotene and vitamin E compared with healthy controls (Uden et al., 1992). Basso aol. (1990) have measured increases in lipid peroxides in the sera of patients with chronic... 

Studies of both acute and chronic pancreatitis in humans and in animals support the hypothesis that free radicals are involved in the pathogenesis of pancreatitis. There is some conflicting data from the animal work, which may in part be due to differences in the models used. It does also indicate that free radicals are not the only factors involved and su ests that activation of pancreatic enzymes are also imprortant, particularly in the development of haemorrhagic pancreatitis (Sanfey, 1991). The findings of decreased antioxidant defences and the success of treatment reported in chronic pancreatitis with a cocktail of antioxidants and with allopurinol surest further studies are required to establish the role of antioxidants in pancreatic disease and its prevention. 

There is very little data on ROM production in haemochromatosis in humans. Increases in thiobarbituric acid reactants in plasma were associated with increases in non-transferrin-bound free iron. However, other indices of lipid peroxidation were no different from controls (Peters eta/., 1985). There are no studies of in vivo lipid peroxidation in humans. It is also of interest that levels of antioxidant defences in liver biopsies from patients with haemochromatosis are normal (Selden et /., 1980). 

Kawase, T., Kato, S. and Lieber, C.S. (1989). Lipid peroxidation and antioxidant defence systems in rat liver after chronic ethanol feeding. Hepatology 10, 815-820. 

It should be remembered that some of the established antioxidants have other metabolic roles apart from free-radical scavenging. The finding of reduced antioxidant defences in diabetes, for example, may not be prima fascie evidence of increased oxidative stress, since alternative explanations may operate. For example, this may reflect a response to reduced free-radical activity as su ested by the results of a previous study (Collier et al., 1988). In the case of ascorbate, an alternative explanation has been proposed by Davis etal. (1983), who demonstrated competitive inhibition of ascorbate uptake by glucose into human lymphocytes. This view is supported by the similar molecular structure of glucose and ascorbic acid (see Fig. 12.4) and by a report of an inverse relationship between glycaemic control and ascorbate concentrations in experimental diabetes in rats. Other investigators, however, have not demonstrated this relationship (Som etal., 1981 Sinclair etal., 1991). 

Aerobes have evolved antioxidant defences to protect... 

Indeed, when present in concentrations sufficient to overwhelm normal antioxidant defences, ROS may be the principal mediators of lung injury (Said and Foda, 1989). These species, arising from the sequential one-electron reductions of oxygen, include the superoxide anion radical, hydrogen peroxide, hypochlorous ions and the hydroxyl radical. The latter species is thought to be formed either from superoxide in the ptesence of iron ions (Haber-Weiss reaction Junod, 1986) or from hydrogen peroxide, also catalysed by ferric ions (Fenton catalysis Kennedy et al., 1989). 

Particulate Reactions 2.1.2 Phagocyte-derived Free 248 2.5.2 Alzheimer s Disease 3. Antioxidant Defence Mechanisms and 252... 

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