Free radical products

The rate of free radical production from Am and B are dependent on the G value of both ... 

Allopurinol 1 mM Xanthine oxidase inhibitor, suppresses oxygen free radical production... 

The mechanism of secondary stabilization by antioxidants is demonstrated in Figure 15.5. TnT-nonylphenyl phosphites, derived from PCI3 and various alcohols, and thio-compounds are active as a secondary stabilizer [21], They are used to decompose peroxides into non-free-radical products, presumably by a polar mechanism. The secondary antioxidant is reacting with the hydroperoxide resulting in an oxidized antioxidant and an alcohol. The thio-compounds can react with two hydroperoxide molecules. 

The slopes, Y-intercepts and squares of correlation coefficients for the linear regression analyses of the T versus AE(ir) plots (equation 7) for reactions 1-4 for one-hour and ten-hour half life rates of decomposition to form free radical products are given in Table II. 

Irons-phenyl, alkyl diazenes (2), peresters (3) and hydrocarbons (4). These equations are intended to be used for their predictive value for applications especially in the area of free radical polymerization chemistry. They are not intended for imparting deep understanding of the mechanisms of radical forming reactions or the properties of the free radical "products". Some interesting hypotheses can be made about the contributions of transition state versus reactant state effects for the structure activity relationships of the reactions of this study, as long as the mechanisms are assumed to be constant throughout each family of free radical initiator. 

The main function of vitamin E is as a chain-breaking, free radical trapping antioxidant in cell membranes and plasma lipoproteins. It reacts with the lipid peroxide radicals formed by peroxidation of polyunsaturated fatty acids before they can establish a chain reaction. The tocopheroxyl free radical product is relatively unreactive and ultimately forms nonradical compounds. Commonly, the tocopheroxyl radical is... 

Morphine and HlV-Tat increase nucrogUal-free radical production and oxidative stress possible role in cytokine regulation. J Neurochem 108 202-215... 

Attention has been given to the possibility that some of the above motor effects may arise from a metabolite of levodopa. The prime suspect is OMD which has a half-life of some 20 hours and reaches plasma concentrations three- to fourfold those of dopa. Suggestions that it may compete with dopa for entry across the blood-brain barrier or act as a partial agonist (effective antagonist) have not been substantiated experimentally although it does reduce DA release from rat striatal slices. Also if free radical production through deamination of DA is neurotoxic (see below) then this would be increased by levodopa. 

Beyer, R.F. (1990). The participation of coenzyme Q in free radical production and antioxidation. Free Rad. Biol. Med. 8, 545-565. 

Figure 4.1 Time-course of free-radical production during aerobic (a) or anoxic (b) reperfusion of the isolated rat heart. Radical production was assessed using e.s.r. and quantified as the formation of a Af-tert-butyl-a-phenylnitrone (PBN) spin adduct. After a 35 min stabilization period of aerobic perfusion, hearts were made globally ischaemic for 15 min. Hearts were then reperfused, either with oxygenated buffer (a) (n = 6), or with anoxic buffer, switching to an oxygenated buffer after 10 min (b) (n = 5). The bars represent the standard errors of the means. Redrawn with permission from Garlick et af. (1987).

During ischaemia, the activity of cellular antioxidant systems may be reduced (Ferrari et al. 1985 GaUnanes etal. 1992). In addition, a number of cellular pathways that produce free radicals are primed during ischaemia such as the xanthine/xanthine oxidase system (McCord, 1987), catecholamine auto-oxidation (Jackson et al., 1986) and the arachadonic acid pathway (Halliwell and Gutteridge, 1989). Thus, during early reperfusion there is a burst of free radical production (see Fig. 4.1) that may overwhelm the antioxidant systems of the cells. 

S-Thiolation of proteins may occur by two main processes as shown in Fig. 4.14. The first relies on an increase in GSSG levels while the second method depends on free radical production and the GSH concentration (Miller et al., 1990). Therefore, it is clear that a significant increase in tissue GSSG levels is not an absolute prerequisite for S-thiolation to occur. 

The most extensive evidence that supports a role for free radicals in pathological conditions of the brain is provided by studies on experimental models of cerebral ischaemia/reperfusion. Although a burst of free-radical production occurs during the reperfusion phase after temporary cerebral ischaemia, the contribution of this radical burst to brain cell death can not be directly quantified. Perhaps the best way to quantify the contribution of free radicals to brain damage after ischaemia/ reperfusion is to assess damage after treatment with free-radical scavengers or antioxidants. Numerous studies have been reported where free-radical scavengers/ antioxidants have been used to try to ameliorate brain... 

Sakomoto, A., Ohnishi, S.T., Ohnishi, T. and Ogawa, R. (1991). Relationship between free radical production and lipid peroxidation during ischemia-reperfusion injury in the rat brain. Brain Res. 554, 186-192. 

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... 

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. 

Chemiluminescence has been used to show increased free-radical production in I/R injury in isolated hepatocytes and in isolated rat livers (Caraceni et al., 1992 Nunes et al., 1992). Studies in isolated rat liver have shown that ischaemia results in increased conversion of... 

Under certain conditions glucose molecules can induce free-radical production (see section on non-enzymatic glycosylation of protein). 

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. 

Albano, E., Lott, K.A.K., Slater, T.F., Stier, A., Symons, M.C.R.and Tomasi, A. (1982). Spin trapping studies on the free radical products formed by metabolic activation of carbon tetrachloride in rat liver microsomal fractions, isolated hepato-cytes and in vivo in the rat. Biochem. J. 204, 593-603. 

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