Phospholipids protection from oxidation

Example 23 Phosphoroamidites containing two tert-hutyl protecting groups. (t-BuO)2PN(z-Pr)2 have been used in many phosphorylation procedures. Konradsson and associates have described a new, efficient route to enantiopure phospholipids starting from (S)-glycidol [39]. R)-his- tert-hu-tyl)-iV,Ar-diisopropylphosphoramidite was used to prepare R)-di-tert-hutyl-phosphoryl glycidol by coupling in the presence of tetrazole (step a) and subsequent oxidation by CPBA (step b). 

Spin trapping has also been applied to the investigation of lipid peroxidation catalysed by myoglobin in linoleate emulsions,204 as well as the oxidation of phospholipids in low-density lipoproteins (18.1) by HOC1.205 Hiramoto et al. have shown that, by quenching the attacking radicals, linoleic acid can protect DNA from oxidation.206 Lipid peroxidation has also been monitored by spin labelling.207... 

Human serum paraoxonase (PON 1) is an esterase that is physically associated with high-density lipoprotein (HDL) and is also distributed in tissues such as liver, kidney, and intestine [38,39]. Activities of PON 1, which are routinely measured, include hydrolysis of organophosphates, such as paraoxon (the active metabolite of the insecticide parathion) hydrolysis of arylesters, such as phenyl acetate and lactonase activities. Human serum paraoxonase activity has been shown to be inversely related to the risk of cardiovascular disease [40,41], as shown in atherosclerotic, hypercholester-olemic, and diabetic patients [42-44]. In 1998 HDL-associated PON 1 was shown to protect LDL, as well as the HDL particle itself, against oxidation induced by either copper ions or free radical generators [45,46], and this effect could be related to the hydrolysis of the specific lipoproteins oxidized lipids such as cholesteryl linoleate hydroperoxides and oxidized phospholipids. Protection of HDL from oxidation by PON 1 was shown to preserve... 

Peroxidation of lipids is another factor which must be considered in the safety evaluation of liposome administration. Smith and coworkers (1983) demonstrated that lipid peroxides can play an important role in liver toxicity. Allen et al. (1984) showed that liposomes protected by an antioxidant caused less MPS impairment than liposomes subjected to mild oxidizing conditions. From the study of Kunimoto et al. (1981) it can be concluded that the level of peroxidation in freshly prepared liposome preparations and those on storage strongly depends both on the phospholipid fatty acid composition and on the head group of the phospholipid. Addition of appropriate antioxidants to liposomes composed of lipids which are liable to peroxidation and designed for use in human studies is therefore necessary. 

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