Peroxidation, lipoprotein lipids

Serban, M. G., and Negru, T., Lipoproteins, lipidic peroxidation and total antioxidant capacity in serum of aged subjects suffering from hyperglycemia. Rom. J. Intern. Med. 36,65-70 (1998). 

NeuzilJ, Thomas SR, Stocker R. Requirement for, promotion, or inhibition by alpha-tocopherol of radical-induced initiation of plasma lipoprotein lipid peroxidation, Free Radic Biol Med 1997 22 57-71. 

Kimura, H., Yamada, Y., Morita, Y., Ikeda, H., and Matsuo, T., 1992, Dietary ascorbic acid depresses plasma and low density lipoprotein lipid peroxidation in genetically scorbutic rats, J. Nutr. 122 1904-1909. 

Turpeinen, A.M., Alfthan, G., Valsta, I., Hietanen, E., Salonen, J.T., Schunk, H., Nyyssdnen, K. and Mutanen, M. 1995. Plasma and lipoprotein lipid peroxidation in humans on sunflower and rapeseed oil diets. Lipids 30 485-490. 

The main function of vitamin E is as a chain-breaking, free radical trapping antioxidant in cell membranes and plasma lipoproteins. It reacts with the lipid peroxide radicals formed by peroxidation of polyunsaturated fatty acids before they can establish a chain reaction. The tocopheroxyl free radical product is relatively unreactive and ultimately forms nonradical compounds. Commonly, the tocopheroxyl radical is... 

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... 

Kim, H.S. and Lee, B.M., Protective effects of antioxidant supplementation on plasma lipid peroxidation in smokers, J. Toxicol. Environ. Health A, 63, 583, 2001. Gaziano, J.M. et al.. Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation. Atherosclerosis, 112, 187, 1995. Sutherland, W.H.F. et al.. Supplementation with tomato juice increases plasma lycopene but does not alter susceptibility to oxidation of low-density lipoproteins from renal transplant recipients, Clin. Nephrol, 52, 30, 1999. 

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

In the previous section, we have described some of the mechanisms that may lead to the fijrmation of lipid hydroperoxides or peroxyl radicals in lipids. If the peroxyl radical is formed, then this will lead to propagation if no chain-breaking antioxidants are present (Scheme 2.1). However, in many biological situations chain-breaking antioxidants are present, for example, in LDL, and these will terminate the peroxyl radical and are consumed in the process. This will concomitandy increase the size of the peroxide pool in the membrane or lipoprotein. Such peroxides may be metabolized by the glutathione peroxidases in a cellular environment but are probably more stable in the plasma comjxutment. In the next section, the promotion of lipid peroxidation if the lipid peroxides encounter a transition metal will be considered. 

Steinbrecher, U.P. (1987). Oxidation of human low density lipoprotein results in derivatisation of lysine residues of apolipoprotein B by lipid peroxidation decomposition products. J. Biol. Chem. 262, 3603-3608. 

Stocker, R., Bowry, V.W. and Frei, B. (1991). Ubiquinol-10 protects human low density lipoprotein more efficiently gainst lipid peroxidation than does a-tocopherol. Proc. Natl Acad. Sci. USA 88, 1646-1650. 

Although atherosclerosis and rheumatoid arthritis (RA) are distinct disease states, both disorders are chronic inflammatory conditions and may have common mechanisms of disease perpetuation. At sites of inflammation, such as the arterial intima undergoing atherogen-esis or the rheumatoid joint, oxygen radicals, in the presence of transition-metal ions, may initiate the peroxidation of low-density lipoprotein (LDL) to produce oxidatively modified LDL (ox-LDL). Ox-LDL has several pro-inflammatory properties and may contribute to the formation of arterial lesions (Steinberg et /., 1989). Increased levels of lipid peroxidation products have been detected in inflammatory synovial fluid (Rowley et /., 1984 Winyard et al., 1987a Merry et al., 1991 Selley et al., 1992 detailed below), but the potential pro-inflammatory role of ox-LDL in the rheumatoid joint has not been considered. We hypothesize that the oxidation of LDL within the inflamed rheumatoid joint plays a pro-inflammatory role just as ox-LDL has the identical capacity within the arterial intima in atherosclerosis. 

Esterbauer et al. (1991) have demonstrated that /3-carotene becomes an effective antioxidant after the depletion of vitamin E. Our studies of LDL isolated from matched rheumatoid serum and synovial fluid demonstrate a depletion of /8-carotene (Section 2.2.2.2). Oncley et al. (1952) stated that the progressive changes in the absorption spectra of LDL were correlated with the autooxidation of constituent fatty acids, the auto-oxidation being the most likely cause of carotenoid degradation. The observation that /3-carotene levels in synovial fluid LDL are lower than those of matched plasma LDL (Section 2.2.2) is interesting in that /3-carotene functions as the most effective antioxidant under conditions of low fOi (Burton and Traber, 1990). As discussed above (Section 2.1.3), the rheumatoid joint is both hypoxic and acidotic. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples (Fairburn etal., 1992). This difference could not be accounted for by the lower concentrations of lipids and lipoproteins within synovial fluid. The low levels of both vitamin E and /3-carotene in rheumatoid synovial fluid are consistent with the consumption of lipid-soluble antioxidants within the arthritic joint due to their role in terminating the process of lipid peroxidation (Fairburn et al., 1992). 

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. 

TBA, thiobarbituric acid reactivity DCs, diene conjugates MA, microangiopathy LP, lipid peroxides DM, diabetic patients C, controls HDL, high-density lipoprotein. 

Nishigaki, 1., Hagjhara, M., Tsunekawa, H., Maseki, M. and Yagi, K. (1981). Lipid peroxide levels of serum lipoprotein fractions of diabetic patients. Biochem. Med. 25, 373-378. 

Steinbrecher, U.P., Parthasarathy, S., Leake, D.S., Witztum, J.L. and Steinberg, D. (1984). Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc. Natl Acad. Sci. USA 81, 3883-3887. 

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). 

Similar to lipids the oxidation of proteins has already been studied for more than 20 years. Before discussing the data on protein oxidation, it should be mentioned that many associated questions were already considered in previous chapters. For example, the oxidation of lipoproteins, which is closely connected with the problems of nonenzymatic lipid peroxidation was discussed in Chapter 25. Many questions on the interaction of superoxide and nitric oxide with enzymes including the inhibition of enzymatic activities of prooxidant and antioxidant enzymes are considered in Chapters 22 and 30. Therefore, the findings reported in those chapters should be taken into account for considering the data presented in this chapter. 

Atherogenic effect. Smoke, administered by inhalation to mice for 10 weeks, produced an increase of lipid peroxidation and a decrease of reduced glutathione level in the heart. Levels of total cholesterol, LDL cholesterol, and triglycerides were increased. The high-density lipoprotein (HDL) cholesterol levels decreased in serum L... 

Fuhrman, B., Lavy, A., and Aviram, M., Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. Am. J. Clin. Nutr., 61, 549, 1995. 

Da Silva, E.L., Tsushida, T., and Terao, J., Inhibition of mammalian 15-lipoxygenase-dependent lipid peroxidation in low-density lipoprotein by quercetin and quercetin monoglucosides. Arch. 

Darley-Usmar, V. M., Hogg, H., O Leary, V. J., Wilson, M. T., and Moncada, S. (1992). The simultaneous generation of superoxide and nitric oxide can initiate lipid peroxidation in human low density lipoprotein. Free Radicals Res. Commun. 17, 9-20. 

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... 

Carbon tetrachloride causes centrilobular liver necrosis and steatosis after acute exposure, and liver cirrhosis, liver tumors, and kidney damage after chronic administration. The mechanism underlying the acute toxicity to the liver involves metabolic activation by cytochrome P-450 to yield a free radical (trichloromethyl free radical). This reacts with unsaturated fatty acids in the membranes of organelles and leads to toxic products of lipid peroxidation including malondialdehyde and hydroxynonenal. This results in hepatocyte necrosis and inhibition of various metabolic processes including protein synthesis. The latter leads to steatosis as a result of inhibition of the synthesis of lipoproteins required for triglyceride export. 

Hazell LJ, Davies MJ, Stocker R (1999) Secondary Radicals Derived from Chloramines of Apolipoprotein B-10 Contribute to HOCl-Induced Lipid Peroxidation of Low-Density Lipoproteins. Biochem J 339 489... 

Sevanian, A. and Ursini, F. (2000) Lipid peroxidation in membranes and low-density lipoproteins similarities and differencesFree Rad. Biol. Med., 29 306-311. 

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