Modification, oxidative

The avermectins also possess a number of aUyflc positions that are susceptible to oxidative modification. In particular the 8a-methylene group, which is both aUyflc and alpha to an ether oxygen, is susceptible to radical oxidation. The primary product is the 8a-hydroperoxide, which has been isolated occasionally as an impurity of an avermectin B reaction (such as the catalytic hydrogenation of avermectin B with Wilkinson s rhodium chloride-triphenylphosphine catalyst to obtain ivermectin). An 8a-hydroxy derivative can also be detected occasionally as a metaboUte (42) or as an impurity arising presumably by air oxidation. An 8a-oxo-derivative can be obtained by oxidizing 5-0-protected avermectins with pyridinium dichromate (43). This also can arise by treating the 8a-hydroperoxide with base. 

The nickel oxide modification obtained electrochemicaHy in KOH electrolyte contained potassium ion and its nickel oxidation level are higher than that of NiO 5. Conclusions regarding the transitions between the reduced and oxidized products within the two series are that the redox process was not reversible and although the oxidized phases of the P- and the y-nickel hydroxides differ in energy contents, differences in analyses and x-ray patterns are not significant. 

Six cycles with oxidant modification are listed as D1 the simple PO open CBT cycle—involving staged combustion of the fuel ... 

In particular, the cycles involving fuel or oxidant modification do not look sufficiently attractive for their development to be undertaken, with the possible exception of the multiple PO combustion plant proposed by Harvey et al. [14]. The Matiant plant has the advantage of relatively simple CO2 removal and high efficiency and may prove to be attractive, but it again looks complex and expensive. 

In the last few decades, several epidemiological studies have shown that a dietary intake of foods rich in natural antioxidants correlates with reduced risk of coronary heart disease particularly, a negative association between consumption of polyphenol-rich foods and cardiovascular diseases has been demonstrated. This association has been partially explained on the basis of the fact that polyphenols interrupt lipid peroxidation induced by reactive oxygen species (ROS). A large body of studies has shown that oxidative modification of the low-density fraction of lipoprotein (LDL) is implicated... 

BROWN M s and goldstein j l (1990) Scavenging for receptors Nature 343, 508-9. ESTERBAUER H, GEBiKi J, PUHL H and JURGENS G (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL Free Radical Biology and Medicine 13, 341-90. 

Jessup, W., Simpson, J.A. and Dean, RT. (1993). Does superoxide radical have a role in macropha mediated oxidative modification of LDL Atherosclerosis 99, 107-120. 

Jialal, 1. and Grundy, S.M. (1992). Effea of dietary supplementation with a-tocopherol on the oxidative modification of LDL. Lipid Res. 33, 899-906. 

Parthasarathy, S., Wieland, E. and Steinberg, D. (1989). A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. Proc. Nad Acad. Sci. USA 86, 1046-1050. 

Sparrow, C.P. and Olszewski, J. (1992). Cellular oxidative modification of low density lipoprotein does not require lipoxygenases. Proc. Natl Acad. Sci. USA 89, 128-131. 

Sparrow, C.P., Parthasarathy, S. and Steinberg, D. (1988). Enzymatic modification of LDL by purified lipoxygenase plus phospholipase Ai mimics cell mediated oxidative modification. J. Lipid Res. 29, 745-733. 

Esterbauer et cil. (1992) have studied the in vitro effects of copper on LDL oxidation and have shown that there are three distinct stages in this process. In the first part of the reaction, the rate of oxidation is low and this period is often referred to as the lag phase the lag phase is apparently dependent on the endogenous antioxidant content of the LDL, the lipid hydroperoxide content of the LDL particle and the fatty acid composition. In the second or propagation phase of the reaction, the rate of oxidation is much faster and independent of the initial antioxidant status of the LDL molecule. Ultimately, the termination reactions predominate and suppress the peroxidation process. The extensive studies of Esterbauer et al. have demonstrated the relative importance of the endogenous antioxidants within the LDL molecule in protecting it from oxidative modification. 

In order to understand the potential for haem proteins to mediate the oxidative modification of LDLs, the interaction between ruptured erythrocytes (Paganga et al., 1992) and ruptured myocytes (Bourne etal., 1994) with LDL has been explored. Previous studies from this group have demonstrated that ferryl myoglobin radicals and ruptured cardiac myocytes, which generate ferryl myoglobin species on activation (Turner et al., 1990,... 

The time-scale of this haem conversion is related to the antioxidant status of the LDL and that of the erythrocyte lysate. The incorporation of lipid-soluble antioxidants, such as tocopherol and butylated hydroxy-toluene (BHT) at specific time points during the LDL-erythrocyte interaction, prolongs the lag phase to oxidation, eliminates the oxy to ferryl conversion of the haemoglobin and delays the oxidative modification of the LDL. 

Palinski, W., Yla-Herttuala, S., Rosenfeld, M.E., Butler, S.W., Socher, S.A., Parthasarathy, S., Curtiss, L.K. and Witztum, J.L. (1990). Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoproteins. Arteriosclerosis 10, 325-335. 

Depletion of the antioxidant capacity of LDL is an early event in the oxidation process. The main antioxidant in LDL is a-tocopherol, with smaller quantities of 0-carotene and 7-tocopherol also present. The importance of antioxidants in inhibiting the oxidative modification of LDL is su ested by human and animal studies on the prevention of atherosclerosis. Preliminary reports... 

Copper salts such as CuS04 are potent catalysts of the oxidative modification of LDL in vitro (Esterbauer et al., 1990), although more than 95% of the copper in human serum is bound to caeruloplasmin. Cp is an acute-phase protein and a potent inhibitor of lipid peroxidation, but is susceptible to both proteolytic and oxidative attack with the consequent release of catalytic copper ions capable of inducing lipid peroxidation (Winyard and... 

Blake, 1989 Winyard et al., 1989). We suggest that within the inflamed rheumatoid joint (or the artery wall in atherogenesis), the production of ROM and proteases by endothelial cells and/or macrophages may cause the release of copper ions from Cp (see Section 2.2.3.2). It has been reported that Cp is cleaved faster in serum from patients with inflammatory diseases when compared to normal serum (Laurell, 1985). The oxidative modification of LDL by Cp-derived copper ions may explain the observation that increased serum cholesterol values are associated with accelerated atherosclerotic progression in men with high serum copper concentrations (Salonen et al., 1991). 

Esterbauer, H., Gebicki, J. Puhl, H. and Jurgens, G. (1992), The role of lipid peroxidation and antioxidants in oxidative modification of low density lipoprotein. Free Rad. Biol. Med. 13, 341-390. 

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