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Ascorbate and phenolic antioxidant interactions in prevention of liposomal oxidation

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Lipids

Abstract

Efficient prevention of membrane lipid peroxidation by vitamin E (α-tocopherol) may involve its regeneration by vitamin C (ascorbate). Conceivably, the efficacy of antioxidants designed as therapeutic agents could be enhanced if a similar regeneration were favorable; thus, a model membrane system was developed which allowed assessment of interaction of phenolic antioxidants with ascorbate and ascorbyl-6-palmitate. Ascorbate alone (50–200 μM) potentiated oxidation of soybean phosphatidylcholine liposomes by Fe2+/histidine-Fe3+, an effect which was temporally related to reduction of Fe3+ generated during oxidation. Addition of 200 μM ascorbate to α-tocopherol-containing liposomes (0.1 mol%) resulted in marked, synergistic protection. Accordingly, in the presence but not absence of ascorbate, α-tocopherol levels were maintained relatively constant during Fe2+/histidine-Fe3+ exposure. Probucol (4,4′-[(1-methylethylidine)bis(thio)]bis[2,6-bis(1,1-dimethylethyl)]phenol), and antioxidant which prevents oxidation of low density lipoproteins, and its analogues MDL 27,968 (4,4′-[(1-methylethylidene)bis(thio)]-bis[2,6-dimethyl]phenol) and MDL 28,881 (2,6-bis(1,1-dimethylethyl)-4-[(3,7,11-trimethyldodecyl)thio]phenol) prevented oxidation but exhibited no synergy with ascorbate. Ascorbyl-6-palmitate itself was an effective antioxidant but did not interact synergistically with any of the phenolic antioxidants. Differential scanning calorimetry revealed significant differences among the antioxidants in their effect on the liquid-crystalline phase transition of dipalmitoyl phosphatidylcholine (DPPC) liposomes. Both α-tocopherol and MDL 27,968 significantly reduced the phase transition temperature and the enthalpy of the transition. MDL 28,881 had no effect while probucol was intermediate. The potential for ascorbate or its analogues to interact with phenolic antioxidants to provide a more effective antioxidant system appears to be dictated by structural features and by the location of the antioxidants in the membrane.

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Abbreviations

BHT:

butylated hydroxytoluene

DPPC:

dipalmitoyl phosphatidylcholine

DSC:

differential scanning calorimetry

EDTA:

ethylenediaminetetraacetic acid

GSH:

reduced glutathione

MDL 27,968:

4,4′-[(1-methylethylidene)bis(thio)]bis[2,6-dimethyl]-phenol

MDL 28,881:

2,6-bis(1,1-dimethylethyl)-4-[3,7,11-trimethyldodecyl)thio]phenol

NADH:

nicotinamide adenine dinucleotide, reduced

probucol:

4,4′[(1-methylethylidene)bis(thio)]bis[2,6-bis(1,1-dimethylethyl)]phenol

TBARS:

thiobarbituric acid reactive substances

Tm :

phase transition temperatures

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Authors and Affiliations

  1. Department of Cardiovascular Diseases, Marion Merrell Dow Research Institute, 2110 E. Galbraith Rd., 45215, Cincinnati, OH

    Craig E. Thomas, Larry R. McLean, Roger A. Parker & David F. Ohlweiler

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  1. Craig E. Thomas
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  2. Larry R. McLean
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  3. Roger A. Parker
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  4. David F. Ohlweiler
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Thomas, C.E., McLean, L.R., Parker, R.A. et al. Ascorbate and phenolic antioxidant interactions in prevention of liposomal oxidation. Lipids 27, 543–550 (1992). https://doi.org/10.1007/BF02536138

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  • DOI: https://doi.org/10.1007/BF02536138

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