Antioxidants mechanisms of actions

Burlakova E B. 1998. Membrane antioxidants. Mechanism of action of antioxidants in ultra-low doses. 

For some time, the effects of and responses to vitamin E have been interpreted in terms of an antioxidant mechanism of action. However, several observations have raised the question as to whether other mechanisms could be involved. For example, the effects of selenium and vitamin E on growth and polyunsaturated fatty acid synthesis in cultured mouse fibroblasts could not be reproduced by artificial antioxidants [198, 199]. The specific requirement of (+ )-a-toco-pherol for the phenotypic differentiation of the rotifer [200] may not be through an antioxidant mechanism. The effects of vitamin E on differentiation of neuroblastoma cells [201] and metamorphosis of various species [202] are likely to be due to a growth-factor-like action. A study on the interaction... 

Another antioxidant mechanism of action is the inhibition of the lipid peroxidation. It can be detected by different methods, but, in most of them, the peroxidation is induced by F enton reaction, in which hydroxyl radicals are generated. Therefore, it would be logical to think that those PPGs that have shown hydroxyl radical scavenging, will be active as lipid peroxidation inhibitors. But it is necessary to develop these kind of assays, because, the absorption properties of these compounds into cells or the ways in which they may offer protection to the exterior of the cell wall, still remain unknown [35]. 

Kulich, D. M. and I R. Shelton (1991) Organosulfur antioxidants Mechanisms of action. 

Vaya J, Aviram M. Nutritional antioxidants mechanisms of action, analyses of activities and medical application. Curr Med Chem 2001 L99-117. 

Probucol. Probucol is an antioxidant that is effective in lowering LDL cholesterol. Whereas probucol was known to lower cholesterol after relatively simple clinical trials (160), its mechanism of action as an antioxidant in the treatment of atherosclerosis is quite novel. Probucol has been shown to have the abiUty to produce regression of atherosclerotic lesions in animal models (161). Probucol therefore represents a novel class of pharmaceutical agent for the treatment of atherosclerosis. This effect occurs mechanistically, in part, by preventing oxidation of LDL, a necessary step in foam cell formation. This antioxidant activity has been shown in laboratory experiments and its activity in lowering LDL cholesterol in human studies is well documented (162). 

Garlic s proven mechanisms of action include (a) inhibition of platelet function, (b) increased levels of two antioxidant enzymes, catalase and glutathione peroxidase, and (c) inhibition of thiol enzymes such as coenzyme A and HMG coenzyme A reductase. Garlic s anti-hyperlipidemic effects are believed to be in part due to the HMG coenzyme A reductase inhibition since prescription medications for hyperlipidemia have that mechanism of action (statins). It is unknown whether garlic would have the same drug interactions, side effects, and need for precautions as the statins. 

Phytochemicals or phytonutrients are bioactive substances that can be found in foods derived from plants and are not essential for life the human body is not able to produce them. Recently, some of their characteristics, mainly their antioxidant capacity, have given rise to research related to their protective properties on health and the mechanisms of action involved. Flavonoids are a diverse group of phenolic phytochemicals (Fig. 6.1) that are natural pigments. One function of flavonoids is to protect plants from oxidative stress, such as ultraviolet rays, environmental pollution, and chemical substances. Other relevant biological roles of these pigments are discussed in other chapters of this book. 

Polyfunctional inhibitors can exert a combined action by participating in different inhibitory reactions. The mixture of antioxidants can act similarly. With respect to the mechanism of action, antioxidants can be divided into the following seven groups [41]. 

Inhibitors slow down oxidation by breaking chains or breaking down hydroperoxide. The inhibitory action of an antioxidant ceases when it is completely consumed. The duration of inhibitory effect depends on the mechanism of action of the antioxidant, the nature of inhibitory reactions, and the occurrence of side reactions in which the inhibitor is uselessly consumed. The action of the antioxidant in a given system can expediently be characterized in terms of inhibitory capacity. The capacity of a chain-breaking inhibitor can be characterized by the inhibition stoichiometric coefficient f[ 18]. 

Metal complexes, dialkyl thiophosphates and dialkyl thiocarbamates of Zn, Ni, Ba, and Ca, in particular, are widely used for the stabilization of lubricants [30-32,34]. At moderate temperatures (350 400 K), these inhibitors are less efficient than phenols, but they are more potent at higher temperatures (430 480 K). The sophisticated mechanism of action of these antioxidants involves their reactions with hydroperoxide. The interaction of hydroperoxide with metal dialkyl thiophosphates induces a cascade of reactions [5,66-69],... 

Synergism of antioxidants was reviewed in the monographs [1-9]. The classification of binary mixtures of inhibitors is based on the mechanisms of action of particular inhibitors [10,11], One of the classification schemes is given in Ref. [11], If one takes into account the... 

Phenol-induced oxidative stress mediated by thiol oxidation, antioxidant depletion, and enhanced free radical production plays a key role in the deleterious activities of certain phenols. In this mode of DNA damage, the phenol does not interact with DNA directly and the observed genotoxicity is caused by an indirect mechanism of action induced by ROS. A direct mode of phenol-induced genotoxicity involves covalent DNA adduction derived from electrophilic species of phenols produced by metabolic activation. Oxidative metabolism of phenols can generate quinone intermediates that react covalently with N-1,N of dG to form benzetheno-type adducts. Our laboratory has also recently shown that phenoxyl radicals can participate in direct radical addition reactions with C-8 of dG to form oxygen (O)-adducts. Because the metabolism of phenols can also generate C-adducts at C-8 of dG, a case can be made that phenoxyl radicals display ambident (O vs. C) electrophilicity in DNA adduction. 

Mecfianism of Action The mechanism of action is not fully understood. Monobenzone maybe converted to hydroquinone, which inhibits the enzymatic oxidation of tyrosine to DOPA it may have a direct action on tyrosinase, or it may act as an antioxidant to prevent SH-group oxidation so that more SH groups are available to inhibit tyrosinase. Therapeutic Effect Depigmentation in extensive vitiligo. 

Mechanism of Action An antioxidant that prevents oxidation of vitamins A and C, protects fatty acids from aff ack by free radicals, and protects RBCs from hemolysis by oxidizing agents. Therapeutic Effect Prevents and treats vitamin E deficiency. Pharmacokinetics Variably absorbed from the GI tract (requires bile salts, dietary fat, and normal pancreatic function). Primarily concentrated in adipose tissue. Metabolized in the liver. Primarily eliminated by biliary system. 

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