Antioxidant Defence Mechanisms

Of all the epidermal cells studied in vitro with respect to antioxidant status, perhaps keratinocytes are the most important. These cells differentiate as they move upwards through the epidermis and there is evidence that, in 

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. 

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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. 

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

Lunec, J. and Blake, D.R. (1988) In Critical Reviews in Chemistry Cellular Antioxidant Defence Mechanisms, Vol. Ill (Ching Quang Chow, Ed.), p. 143, CRC Press, Boca Raton, FL. 

Hager K, Marahrens A, Kenklies M, Riederer P, Munch G (2001) Alpha-Upoic add as a new treatment option for Azheimer type dementia. Arch Gerontol Geriatr 32 275-282 HalliweU B (1999) Antioxidant defence mechanisms from the beginning to the end (of the beginning). Free Radic Res 31 261-272... 

There is considerable body of (indirect) evidence which makes oxidative stress one of the best accepted hypothesis for explaining the cause of Parkinson s disease. For example, the Fe(II)/Fe(III) ratio in the substantia nigra is shifted from 2 1 in the normal brain to 1 2 in Parkinsonian brain.131,132 In the Parkinsonian brain several enzymes which constitute the antioxidative defence mechanisms (glutathione peroxidase, catalase) have a decreased activity, while the activity of superoxide dismutase is increased, relative to the normal brain.133 Furthermore, specific products of radical damage, such as lipid hydroperoxides, were detected at a 10-fold increased level in the Parkinsonian brain.134... 

Benzie IF. (2000) Evolution of antioxidant defence mechanisms. Eur J Nutr 39 53-61. 

Vericel, E., Narce, M., Ulmann, L., Poisson, J. P., and Lagarde, M. Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats. Mol Cell Biochem 132 (1994) 25-29. 

Oxidative stress is a condition in which free radicals and their products are present in excess of antioxidant defence mechanisms, leading to oxidative damage and structural and functional modifications of proteins, DNA, and RNA. Radicals can be formed through different mechanisms. ROS are formed by the reduction of molecular oxygen to water superoxide (O "), peroxyl radical (OH ), and hydrogen peroxide (H O ). RNS (NO and peroxynitrite) can also cause oxidative stress. 

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. 

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. 

Since glutathione reductase is a cornerstone of the malaria parasite antioxidant defence and repair mechanism, it is a potential target for antimalarial and cytostatic agents. 

A sophisticated respiratory host defence system has evolved to clear airborne particles and potential pathogens in inspired air [106, 143], The system comprises mechanical (i.e. air filtration, cough, sneezing and mucociliary clearance), chemical (antioxidants, antiproteases and surfactant lipids) and immunological defence mechanisms and is tightly regulated to minimise inflammatory reactions [92, 143],... 

Superoxide dismutases (SOD EC 1.15.1.1) constitute a group of metalloisoenzymes that neutralise the very reactive superoxide radical, generated in the cell as a by-product of the reduction of molecular oxygen (Salin, 1988). SOD is a highly efficient enzyme system involved in the cellular antioxidant system (cf. section on defence mechanisms). 

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