Antioxidant activities agents

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). 

In addition to phenolic substances, there are other components present in foods which have no antioxidant activity of their own, but which increase that of phenolic antioxidants. They are called synergists, and they should be accounted for in any discussion of antioxidant activity. Polyvalent organic acids, amino acids, phospholipids (lecithin) and various chelating agents belong to this group. Proteins may modify the efficiency of antioxidants as they react with the reaction products of both antioxidants and synergists. 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

There are numerous other polyphenolic compounds possessing in vitro and in vivo antioxidative activity. Several examples of these compounds are cited below. One of nonflavonoid polyphenols of particular interest is resveratrol (3,5,4 -trihydroxy-Znmv-stilbcne, Figure 29.8), which has been identified as a potential cancer chemopreventive agent and an antimutagen [182]. It has been found that resveratrol is the efficient inhibitor of cyclooxygenase and the inhibitor of free radical-mediated cellular processes. For example, resveratrol is a better free radical scavenger than a-tocopherol or ascorbic acid but has nearly the same activity as... 

Contemporary interest in ubiquinones is explained by their potential antioxidant activity and the possibility of using these nontoxic natural compounds as pharmaceutical agents. But it should be noted that ubiquinones are not vitamins and that they are synthesized in humans. Taking into account a high level of ubiquinones in mitochondria, the effective supplementation of ubiquinones to fight against free radical-mediated damage seems to be a hard task. 

Ponka et al. [372] showed that pyridoxal isonicotinoyl hydrazone (PIH, Figure 19.23) is an iron chelating agent. Numerous studies showed the possibility of using this chelator for the treatment of iron overload disease [373], In subsequent studies the antioxidant activity of PIN has been confirmed. For example, Hermes-Lima et al. [374,375] showed that PIN protected plasmid pUC-18 DNA and 2-deoxyribose against hydroxyl radical damage. 

It has long been suggested that ROS may play causal roles in these diseases and in the production of the aberrant protein molecules (de Arriba et al., 2006). In addition, protein damage inflicted by RNS has also been suggested. As discussed above, carnosine has been shown to possess antioxidant activity and also to react with RNS as well, hence the molecule has the potential to be considered as a theraupeutic agent (Calabrese et al., 2008). 

New uses of known products may be patented. Thus, if protein X is only known for use as and anti-coagulant agent, claims directed to its use in an application based on the finding that it has antioxidant activity, would be novel. 

Additional uses for higher olefins include the production of epoxides for subsequent conversion into surface-active agents, alkylation of benzene to produce drag-flow reducers, alkylation of phenol to produce antioxidants, oligomerization to produce synthetic waxes (qv), and the production of linear mercaptans for use in agricultural chemicals and polymer stabilizers. Aluminum alkyls can be produced from heavy olefin streams and olefin or paraffin streams have been sulfaled or sulfonated and used in the leather (qv) industry. 

Shelf stability of a product is of critical importance because it is affected by longterm antimicrobial and antioxidizing activity enhanced by preservative agents compared to only antimicrobial agents that are added to dressings for thwarting infection in a wound. Preferably, a preservative can be added to a product that possesses broad-spectrum antimicrobial activity that will allow the product to maintain activity before reaching a planned expiration date, and prevent infection when applied to wounds. 

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