Peroxidation, of lipids

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. 

Peroxidation of lipids containing polyunsaturated fatty acids leads to generation of free radicals that may damage tissues and cause disease. 

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). 

Morel, D.W., Hessler, J.R. and Chisolm, G.M. (1983a). Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid. J. Lipid Res. 24, 1070-1076. 

Wrona, M, Rozanowska, M, and Sarna, T, 2004. Zeaxanthin in combination with ascorbic acid or alpha-tocopherol protects ARPE-19 cells against photosensitized peroxidation of lipids. Free Radic Biol Med 36, 1094-1101. 

The basic structure of carotenoids is a conjugated polyprenoid chain. Carotenoids exert a positive impact on human welfare. They show marked singlet molecular oxygen quenching capacity [11] and they protect against photosensitized peroxidation of lipids [12],... 

Increase of free cytosolic calcium is toxic for various reasons. Among them are the diminution of ATP levels (Tsuji et al. 1994), the protease and lipase activation, and the FR production that causes a peroxidation of lipids. The inflow of calcium in the terminals could also increase the release of endogenous excitatory amino acids and propagate neuronal damage through positive feedback (Choi and Hartley 1993). Glutamic neurotoxicity mediated by calcium follows three stages ... 

Ethylene is rather inert, but it is metabolized slowly, some of it to ethylene glycol.326 Plants store N-malonyl-ACC as a metabolically inert pool. Excess ACC can be deaminated in a PLP-dependent reaction to 2-oxobutyrate (step k, Fig. 24-16), a process that also occurs in bacteria able to subsist on ACC.327/327a There may also be other mechanisms for ethylene formation, e.g., peroxidation of lipids during scenescence of leaves.328 See also Chapter 31, Section G. 

Rudneva-Titova, I.I. (1995). Lipid content and peroxidation of lipid in the blood serum of Black Sea cartilaginous and bony fishes (In Russian). Zhumal Evolutsionnoy Biokhimii i Physiologii 31,14—20. 

Figure 10.8 Peroxidation of lipid molecules by reactive radical species such as the hydroxyl radical, HO.

Many studies of melatonin are accompanied on an idea that many of the effects credited to melatonin may be mediated by some melatonin analogues or metabolites [138], such as by AFMK, a product of the melatonin antioxidant cascade, which is also a potent scavenger of reactive species [139]. Also, the melatonin precursor, N-acetylserolonin, or the melatonin metabolite 6-hydroxymelatonin, which was found a better antioxidant than melatonin itself by authors Zhang and coworkers [140], is considered Melatonin-related indoles that protect and defend against both autooxidation and iron-induced peroxidation of lipids [141]. 

Vitamin E (tocopherol) possesses antioxidative properties, which means it can protect polyunsaturated fatty acids from auto-oxidation. Deficiency of vitamin E causes increased peroxidation of lipids, which consequently leads to elevated production of prostaglandins. Increased concentration of prostaglandins, in turn, retards... 

Virantmycin (119) isolated from S. nitrosporeus [103] exhibits an antiviral activity [104] and a weak antifungal activity. It prevents peroxidation of lipids in rat liver microsomes. In the cell assay, benzastatins C and D inhibited glutamate toxicity in N 18-RE-105 cells with EC50 values of 2.0 and 5.4 pM, respectively [105]. Pyrroxamycin (98) isolated from an unidentified streptomycete [106] was found to inhibit Gram-positive bacteria and dermatophytes. 

Radicals generated during peroxidation of lipids and proteins show reactivity similar to that of the hydroxyl radical however, their oxidative potentials are lower. It is assumed that the reactive alkoxyl radicals rather than the peroxyl radicals play a part in protein fragmentation secondary to lipid peroxidation process, or protein exposure to organic hydroperoxides (DIO). Reaction of lipid radicals produces protein-lipid covalent bonds and dityrosyl cross-links. Such cross-links were, for example, found in dimerization of Ca2+-ATPase from skeletal muscle sarcoplasmic reticulum. The reaction was carried out in vitro by treatment of sarcoplasmic reticulum membranes with an azo-initiator, 2,2/-azobis(2-amidinopropane) dihydrochloride (AAPH), which generated peroxyl and alkoxyl radicals (V9). 

These initial steps are highly exothermic, which accelerates the autoxidation cycle to an explosive rate to give CO, CO2, and H2O as the stable products. Within biological matrices the autoxidation and peroxidation of lipids and fats from foodstuffs are important examples of oxygen radical... 

The antioxidant properties of estrogens have been demonstrated in many in vitro and in vivo studies. For instance, estrogens inhibit the oxidation of LDL, the peroxidation of lipids, and the oxidation of cholesterol. The administration of 17p-estradiol to ovariecto-mized pigs inhibits the oxidation of LDL. This effect has also been observed in postmenopausal women after administration of 17p-estradiol. These antioxidant activities of estrogens are believed to explain the lower rate of heart disease in premenopausal women, or postmenopausal women treated with estrogen, compared to that of men. ... 

Fats or raw materials that serve as a source for fatty acids are frequently employed in process flavourings. During the flavour reaction, thermal peroxidation of lipids such as triglycerides, fatty acids and phospholipids occurs. This non-enzymatic lipid oxidation, also called autoxidation, leads to a very complex mixture of reaction products, and has to be regarded separately from the enzymatic lipid oxidation which occurs at low temperature and is catalysed by lipoxygenases. 

The concentrations at which atmospheric pollutants cause irreversible changes in the vegetal cell after 30 minutes and 4 hours of exposure were estimated experimentally. Fresh leaves of laboratory plants were used to study die relationships between the concentration of individual pollutants in the fumigation chamber and die peroxide activity, the intensity of peroxidation of lipids and the content of photo-syndietic pigments in the vegetal cell. 

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