Lipid hydroperoxy radical

Not all oxidants formed biolc cally have the potential to promote lipid peroxidation. The free radicals superoxide and nitric oxide [or endothelium-derived relaxing aor (EDRF)] are known to be formed in ww but are not able to initiate the peroxidation of lipids (Moncada et tU., 1991). The protonated form of the superoxide radical, the hydroperoxy radical, is capable of initiating lipid peroxidation but its low pili of 4.5 effectively precludes a major contribution under most physiological conditions, although this has been suggested (Aikens and Dix, 1991). Interestingly, the reaction product between nitric oxide and superoxide forms the powerful oxidant peroxynitrite (Equation 2.6) at a rate that is essentially difiiision controlled (Beckman eta/., 1990 Huie and Padmaja, 1993). 

The now classic Farmer-type hydrogen-abstraction Initiation of free radical autoxldatlon accounts for a large portion of the nonenzymlc oxidations of n-3 fatty acids (45). Because fish lipids contain substantial concentrations of EPA and DHA (47-48), they provide many allowed sites (18, 22, 45, 46, 49) of hydroperoxide formations, and thus can account for a large array of decomposition products. Oxidizing model systems of unsaturated methyl esters of fatty acids yielded monohydroperoxides, but also produce dlhydroperoxldes that are formed by cycllzatlon of Intermediate hydroperoxy radicals when suitable H-donatlng antioxidants are not present to quench the free radical reaction (45, 50, 51). Decomposition of monohydroperoxides of fatty acids In model systems yields a very different profile of lower molecular weight products than observed for similar decompositions of dlhydroperoxldes of the same fatty acids (45, 46). 

Reactive free radicals extract electrons (usually as hydrogen atoms) from other compounds to complete their own orbitals, thereby initiating free radical chain reactions. The hydroxyl radical is probably the most potent of the ROS. It initiates chain reactions that form lipid peroxides and organic radicals and adds direcdy to compounds. The superoxide anion is also highly reactive, but has limited hpid solubility and cannot diffuse far. However, it can generate the more reactive hydroxyl and hydroperoxy radicals by reacting nonenzymatically with hydrogen peroxide in the Haber-Weiss reaction (Fig 24.4). 

They postulated that the initiating event was a radical addition of a hydroxyl (or lipid oxy) radical to the indole ring however, others (33, 34) have demonstrated that formation of a hydroperoxy group at carbon-3 of the indole ring was intermediate in the oxidation of indole derivatives by various oxidants. This latter pathway seems a more plausible route to the products observed by Yong et al. (32). Schaich and Karel... 

Reactions of Vitamin E with Lipid Hydroperoxy and Alkoxy Radicals... 

Figure 45-6. Interaction and synergism between antioxidant systems operating in the lipid phase (membranes) of the cell and the aqueous phase (cytosol). (R-,free radical PUFA-00-, peroxyl free radical of polyunsaturated fatty acid in membrane phospholipid PUFA-OOH, hydroperoxy polyunsaturated fatty acid in membrane phospholipid released as hydroperoxy free fatty acid into cytosol by the action of phospholipase Aj PUFA-OH, hydroxy polyunsaturated fatty acid TocOH, vitamin E (a-tocopherol) TocO, free radical of a-tocopherol Se, selenium GSH, reduced glutathione GS-SG, oxidized glutathione, which is returned to the reduced state after reaction with NADPH catalyzed by glutathione reductase PUFA-H, polyunsaturated fatty acid.)...

Free radicals are by-products of prostaglandin metabolism and may even regulate the activity of the arachidonate pathway. Arachidonic acid, released from lipids as a result of activation of phospholipases by tissue injury or by hormones, may be metabolized by the prostaglandin or leu-kotriene pathways. The peroxidase-catalysed conversion of prostaglandin G2 to prostaglandin H2 (unstable prostanoids) and the mechanism of hydroperoxy fatty acid to the hydroxy fatty acid conversion both yield oxygen radicals, which can be detected by e.s.r. (Rice-Evans et al., 1991). 

Schnurr et al. [22] showed that rabbit 15-LOX oxidized beef heart submitochondrial particles to form phospholipid-bound hydroperoxy- and keto-polyenoic fatty acids and induced the oxidative modification of membrane proteins. It was also found that the total oxygen uptake significantly exceeded the formation of oxygenated polyenoic acids supposedly due to the formation of hydroxyl radicals by the reaction of ubiquinone with lipid 15-LOX-derived hydroperoxides. However, it is impossible to agree with this proposal because it is known for a long time [23] that quinones cannot catalyze the formation of hydroxyl radicals by the Fenton reaction. Oxidation of intracellular unsaturated acids (for example, linoleic and arachidonic acids) by lipoxygenases can be suppressed by fatty acid binding proteins [24]. 

The most widely used antioxidants are free radical scavengers that remove reactive radicals formed in the initiation and propagation steps of autoxidation. A number of natural or synthetic phenols can compete, even at low concentrations, with lipid molecules as hydrogen donors to hydroperoxy and alkoxy radicals, producing hydroperoxides and alcohols and an unreactive radical. (3-carotene reacts with per-oxy radicals, producing a less-reactive radical. These stabilized radicals do not initiate or propagate the chain reaction. 

Oxidative cellular damage by reactive oxygen species such as superoxide anion, hydroperoxy and hyassociated with various human chronic diseases, e.g. cancers, inflammation, arthritis, atherosclerosis and also with the process of ageing. Claims that diet and increased intake of nutrients exhibiting antioxidative activity have a preventative effect on chronic diseases have increased in recent years. In this context, polyphenolic compounds such as tannins, flavonoids, coumarins, lignans and caffeic acid derivatives, which are abundantly contained in a large number of medicinal plants, foods and beverages, are of particular interest for human health care because of the antioxidative properties widely found in plant phenolics. The antioxidative activity of tannins has been extensively studied in various in vitro and in vivo experimental systems and summarized in reviews [96, 97]. Such activity includes the inhibition of lipid peroxidation induced by NADPH-ADP and ascorbic acid-ADP in rat liver microsomes and mitochondria, respectively... 

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