Oxidation by Antioxidants

The enumerated experiments give evidence of a complex mechanism of the action of antioxidants. We might think that the latter not only terminate the reaction chains, but can also initiate oxidation. If an antioxidant only terminates the chains, then its introduction into the polymer cannot lead to a reduction of the induction period. If it possesses the ability to terminate and initiate the chain, on the other hand, then its addition under certain conditions can lead to a reduction of the induction period. 

In order to realize the latter case, we introduced 0.02 mole/kg di-tert-butyl-p-cresylmethane into polypropylene, which increased the induction period to 180 min at 200°C and po, = 300 mm Hg. If another antioxidant, 2,6-di-tert-octyl-4-methylphenol, is added to polypropylene thus stabilized, the induction period is reduced from 180 to 50 min [33] 

The presence of initiation of oxidation by antioxidants also permits us to explain the fact that the induction period does not increase linearly, but more slowly when the concentration of the inhibitor increases (Fig. 18). 

It is clear that the effectiveness of an antioxidant depends on the ratio of the rates of chain termination and initiation. Since the latter process is characterized by a greater activation energy, when the temperature increases, the rate of initiation increases more rapidly than the rate of chain termination. Hence the effectiveness of an antioxidant should decrease with increasing temperature, which is actually observed experimentally. 

Initiation can occur as a result of oxidation of the inhibitor according to the reaction 

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Convincing evidence indicates that ROS generated both endogenously and also in response to diet and lifestyle factors may play a significant role in the etiology of atherosclerosis and CHD. Indeed, free radicals are responsible for LDL oxidation, which is involved in the initiation and promotion of atherosclerosis. Thus, protection from LDL oxidation by antioxidants such as carotenoids may lead to protection against human CHD. 

Esterbauer, H., Waeg, G., Puhl, H., Dieber-Rotheneder, M. and Tatzber, F. (1992). Inhibition of LDL oxidation by antioxidants. In Free Radicals and Aging (eds. I. Emerit and B. Chance) pp. 145-157. Birkhauser Verlag, Basel. 

Potent inhibition of PGH synthase-dependent BP oxidation by antioxidants suggests that the quinones are products of free radical reactions (18 ). ... 

Inhibition of Protein Oxidation by Antioxidants and Free Radical Scavengers... 

INHIBITION OF PROTEIN OXIDATION BY ANTIOXIDANTS AND FREE RADICAL SCAVENGERS... 

The prevention of LDL oxidation by antioxidants has been viewed as an important potential means of decreasing the risk of heart disease. Plant phenolic antioxidants in fruits and beverages (wine, grapes, grape juice and tea)... 

Because plastics are protected against oxidation by antioxidants, see Chapter 3, the effectiveness of the antioxidants is evaluated to determine the oxidative resistance of stabilized polymers. 

Rubber Chemicals. Sodium nitrite is an important raw material in the manufacture of mbber processing chemicals. Accelerators, retarders, antioxidants (qv), and antiozonants (qv) are the types of compounds made using sodium nitrite. Accelerators, eg, thiuram [137-26-8J, greatly increase the rate of vulcaniza tion and lead to marked improvement in mbber quaUty. Retarders, on the other hand (eg, /V-nitrosodiphenylamine [156-10-5]) delay the onset of vulcanization but do not inhibit the subsequent process rate. Antioxidants and antiozonants, sometimes referred to as antidegradants, serve to slow the rate of oxidation by acting as chain stoppers, transfer agents, and peroxide decomposers. A commonly used antioxidant is A/,AT-disubstituted Nphenylenediamine which can employ sodium nitrite in its manufacture (see Rubber chemicals). 

Biological Antioxidant Models. Tea extracts, tea polyphenol fractions, and purified catechins have all been shown to be effective antioxidants in biologically-based model systems. A balance between oxidants and antioxidants is critical for maintenance of homeostasis. Imbalances between free radicals and antioxidants may be caused by an increased production of free radicals or decreased effectiveness of the antioxidants within the reaction system. These imbalances can be caused by the radicals overwhelming the antioxidants within the system, or by an excess of antioxidants leading to a prooxidant functionaHty (105—118). When antioxidant defense systems are consistently overwhelmed by oxidative reactions, significant damage can... 

Radical Scavengers Hydrogen-donating antioxidants (AH), such as hindered phenols and secondary aromatic amines, inhibit oxidation by competing with the organic substrate (RH) for peroxy radicals. This shortens the kinetic chain length of the propagation reactions. 

Polyisobutylene has the chemical properties of a saturated hydrocarbon. The unsaturated end groups undergo reactions typical of a hindered olefin and are used, particularly in the case of low mol wt materials, as a route to modification eg, the introduction of amine groups to produce dispersants for lubricating oils. The in-chain unsaturation in butyl mbber is attacked by atmospheric ozone, and unless protected can lead to cracking of strained vulcanizates. Oxidative degradation, which leads to chain cleavage, is slow, and the polymers are protected by antioxidants (75). 

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

Propyl gallate is an antioxidant. It protects against oxidation by hydrogen peroxide and oxygen free radicals in a catalytic manner similar to superoxide dismutase. 

Polyisobutylene and IIR have chemical resistance expected of saturated hydrocarbons. Oxidative degradation is slow and the material may be further protected by antioxidants, for example, hindered phenols. 

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. 

Gieseg, S.P., Maghzal, G., and Glubb, D., Protection of erythrocytes by the macrophage synthesized antioxidant 7,8 dihydroneopterin. Free Radic. Res., 34, 123, 2001. Gieseg, S.P. and Cato, S., Inhibition of THP-1 cell-mediated low-density lipoprotein oxidation by the macrophage-synthesised pterin, 7,8-dihydroneopterin, Redox Rep., 8, 113, 2003. 

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

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