Lipids, peroxidation in biomembranes

Kagan, V.E., 1988, Lipid peroxidation in biomembranes, ppl-146, CRC Press, Boca Raton, FL. 

Inhibition of peroxidation of unsaturated lipid chains in biomembranes is of particular significance and interest, because uncontrolled oxidation disrupts the protective layer around cells provided by the membranes. Furthermore, radical chain transfer reactions can also initiate damage of associated proteins, enzymes and DNA. The volume of literature is immense and expanding in the field of antioxidants. We will select certain milestones of advances where micelles and lipid bilayers, as mimics of biomembranes, provided media for quantitative studies on the activities of phenolic antioxidants. One of us, L. R. C. Barclay, was fortunate to be able to spend a sabbatical in Dr. Keith Ingold s laboratory in 1979-1980 when we carried out the first controlled initiation of peroxidation in lipid bilayers of egg lecithin and its inhibition by the natural antioxidant a-Toc . A typical example of the early results is shown in Figure 4. The oxidizability of the bilayer membrane was determined in these studies, but we were not aware that phosphatidyl cholines aggregate into reverse micelles in non-protic solvents like chlorobenzene, so this determination was not correct in solution. This was later corrected by detailed kinetic and P NMR studies, which concluded that the oxidizability of a lipid chain in a bilayer is very similar to that in homogeneous solution . ... 

Oxygenated acylglycerols. Lipid peroxidation in biological tissues attracts much attention because of its possible contribution to the functional modulation of biomembranes and lipoproteins. It is believed to be involved in free-radical-mediated damage, carcinogenesis and ageing processes. Research requires specific, sensitive and reproducible procedures to quantify the lipid hydroperoxides in each lipid class as primary products and the alcohols and aldehydes as secondary products of the peroxidation reaction. The identification and quantification of lipid oxidation products is therefore of great practical and theoretical interest and MS has assumed a major role in these analyses as a result of the development of mild ionization techniques. 

Nevertheless, several reports have suggested that the application of large amounts of ascorbic acid can indeed be effective in protecting neurons against insults in vivo. It has been postulated that in ischemia, cell damage is due to lipid peroxidation of biomembranes induced by oxygen free radicals (Flamm et al.,... 

Beuge, J.A. Aust, S.D. (1978). Microsomal lipid peroxidation. In Methods in Enzymology Biomembranes, Vol. Ell (eds S. Fleischer L. Packer), pp. 302-310. Academic Press, New York. 

Barclay LRC, Baskin KA, Locke SJ, Vinquist MR (1989) Absolute rate constants for lipid peroxidation and inhibition in model biomembranes. Can J Chem 67 1366-1369 Bartlett PD, Guaraldi G (1967) Di-t-butyl trioxide and di-t-butyl tetroxide. J Am Chem Soc 89 4799-4801... 

Aside from oxidized nucleic acids, radical-mediated damage to cellular biomembranes results in lipid peroxidation, a process that genraates a variety of products including reactive electrophiles such as epoxides and aldehydes (JauCTo... 

The surface-active properties of phospholipids (PL) are widely used for the formation of liposomes, which are a model of biomembranes and also a technique for the study of cells and exposure to them [1,2], Earlier it has been established the substantial role of lipids which contain in biosorbents for the regulation of properties of lipids in medium [3], It was also foimd that scale and character of interrelations between the different fractions in lipids of the mice tissue had a dependence on physicochemical properties of lipids [4, 5], and the physicochemical properties and composition of natural lipids have an influence on those of liposomes formed from them [6]. Besides, earlier it was shown the existence of physicochemical regulatory system of the lipid peroxidation (LPO) both a membrane and organ levels [7, 8]. It allows us to suggest the existence of a uniform mechanism of the regulatory in the LPO system both on the membrane and the organ levels. 

In fact, the loss of ascorbate due to metal-catalyzed oxidation may be of subordinate relevance compared to the toxicity of the simultaneously generated OH radical. Mixtures of ascorbate and transition metals were shown to induce high amplitude swelling of mitochondria (Hunter et al., 1964), a phenomenon later shown to be associated with oxidative biomembrane destruction (Flohe and Zim-mermann, 1974). Combinations of Fe2+ and ascorbate later became a routine tool to induce lipid peroxidation (Gutteridge et al., 1979 Aust et al., 1985). Intra-... 

It remains uncertain, however, whether oxidative alterations of biomembranes exerted by ascorbate is related to toxicity rather than to physiological events. Ohyashiki et al. (1994) followed the Fe +Zascorbate/t-butyl hydroperoxide-induced oxidation of membrane thiols, a consequence of massive lipid peroxidation, by the incorporation of fluorescence dyes. The thiol reactivity of the membrane proteins appeared to change characteristically before and after a critical level of lipid peroxidation occurred. If lipid peroxidation and oxidation of membrane thiols are indeed involved in various ascorbate effects, a shift from benefit to toxicity observed in ascorbate-treated cultured cells might just represent two sides of the same coin. 

Although phospholipid bilayers are better mimics of biomembranes than are micelles, there are few reliable quantitative data on flavonoid antioxidant activities in lipid bilayers. Terao and coworkers compared the antioxidant efficiency of quercetin and catechins (epicatechin and epicatechin gallate) with that of a-Toc in egg yolk PC liposomes using initiation by the water-soluble initiator, ABAP, and analysis of hydroperoxide formation and antioxidant consumption by HPLC. Based on the length of the induction periods and the profile of suppressed hydroperoxide formation, they concluded that quercetin and the catechins were more efficient antioxidants than a-Toc in these bilayers. Apparently the unique behavior of a-Toc in bUayers is responsible for these results (vide supra). In hexane and alcohols solution during suppressed peroxidation of methyl linoleate, the relative antioxidant activities reversed so that the flavonoids were 5-20 times less active... 

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