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Ascorbate and phenolic antioxidant interactions in prevention of liposomal oxidation

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Lipids

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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

References

  1. Burton, G.W., Joyce, A., and Ingold, K.U. (1983)Arch. Biochem. Biophys. 221, 281–290.

    Article  PubMed  CAS  Google Scholar 

  2. Liebler, D.C., Kaysen, K.L., and Kennedy, T.A. (1989)Biochemistry 28, 9772–9777.

    Article  PubMed  CAS  Google Scholar 

  3. Liebler, D.C., Baker, P.F., and Kaysen, K.L. (1990)J. Am. Chem. Soc. 112, 6995–7000.

    Article  CAS  Google Scholar 

  4. Liebler, D.C., Kaysen, K.L., and Burr, J.A. (1991)Chem. Res. Toxicol. 4, 89–93.

    Article  PubMed  CAS  Google Scholar 

  5. Groger, Jr., E.H., and Tappel, A.L. (1971)Lipids, 6, 147–148.

    Article  Google Scholar 

  6. Ingold, K.U., Burton, G.W., Foster, D.O., Hughes, L., Lindsay, D.A., and Webb, A. (1987)Lipids 22, 163–172.

    Article  PubMed  CAS  Google Scholar 

  7. Reddy, C.C., Scholz, R.W., Thomas, C.E., and Massaro, E.J. (1982)Life Sci. 31, 572–575.

    Article  Google Scholar 

  8. Leedle, R.A., and Aust, S.D. (1990)Lipids, 25, 241–245.

    PubMed  CAS  Google Scholar 

  9. Yonaha, M., and Tampo, Y. (1987)Biochem. Pharmacol. 36, 2831–2837.

    Article  PubMed  CAS  Google Scholar 

  10. Tirmenstein, M.A., and Reed, D.J. (1988)Arch. Biochem. Biophys. 261, 1–11.

    Article  PubMed  CAS  Google Scholar 

  11. Packer, L., Maguire, J.J., Mehlhorn, R.J., Serbinova, E., and Kagan, V.E. (1989)Biochem. Biophys. Res. Commun. 159, 229–235.

    Article  PubMed  CAS  Google Scholar 

  12. Tappel, A.L. (1968)Geriatrics 23, 97–105.

    PubMed  CAS  Google Scholar 

  13. Packer, J.E., Slater, T.F., and Willson, R.F. (1979)Nature 278, 737–739.

    Article  PubMed  CAS  Google Scholar 

  14. Mukai, K., Nishimura, M., and Kikuchi, S. (1991)J. Biol. Chem. 266, 274–278.

    PubMed  CAS  Google Scholar 

  15. Doba, T., Burton, G.W., and Ingold, K.U. (1985)Biochim. Biophys. Acta 835, 298–303.

    PubMed  CAS  Google Scholar 

  16. Sato, K., Niki, E., and Shimasaki, H. (1990)Arch. Biochem. Biophys. 279, 402–405.

    Article  PubMed  CAS  Google Scholar 

  17. Burton, G.W., Doba, T., Gabe, E.J., Hughes, L., Lee, F.L., Prasad, L., and Ingold, K.U. (1985)J. Am. Chem. Soc. 107, 7053–7065.

    Article  CAS  Google Scholar 

  18. Kagan, V.E., Serbinova, E., Bakalova, R.A., Stoytchev, T.S., Erin, A.N., Prilipko, L.L., and Evstigneeva, R.P. (1990)Biochem. Pharmacol. 40, 2403–2413.

    Article  PubMed  CAS  Google Scholar 

  19. Mukai, K., Nishimura, M., Ishizu, K., and Kitamura, Y. (1989)Biochim. Biophys. Acta 991, 276–279.

    PubMed  CAS  Google Scholar 

  20. Barnhart, R.L., Busch, S.J., and Jackson, R.L. (1989)J. Lipid Res. 30, 1703–1710.

    PubMed  CAS  Google Scholar 

  21. Mao, S.J.T., Yates, M.T., Rechtin, A.E., Jackson, R.L., and Van Sickle, W.A. (1991)J. Med. Chem. 34, 298–302.

    Article  PubMed  CAS  Google Scholar 

  22. Kita, T., Nagano, Y., Yokode, M., Ishii, K., Kume, N., Ooshima, A., Yoshida, H., and Kawai, C. (1987)Proc. Natl. Acad. Sci. USA 84, 5928–5931.

    Article  PubMed  CAS  Google Scholar 

  23. Carew, T.E., Schwenke, D.C., and Steinberg, D. (1987)Proc. Natl. Acad. Sci. USA 84, 7725–7729.

    Article  PubMed  CAS  Google Scholar 

  24. Neuworth, M.B., Laufer, R.J., Barnhart, J.W., Sefranka, J.A., and McIntosh, D.D. (1970)J. Med. Chem. 13, 722–725.

    Article  PubMed  CAS  Google Scholar 

  25. Kremer, J.M.H., v.d. Esker, M.W.J., Pathmamanoharan, C., and Wiersema, P.H. (1977)Biochemistry 16, 3932–3935.

    Article  PubMed  CAS  Google Scholar 

  26. Buege, J.A., and Aust, S.D. (1978)Methods Enzymol. 52, 302–310.

    PubMed  CAS  Google Scholar 

  27. Warren, D.L., and Reed, D.J. (1991)Arch. Biochem. Biophys. 285, 45–52.

    Article  PubMed  CAS  Google Scholar 

  28. Minotti, G., and Aust, S.D. (1987)Free Rad. Biol. Med. 3, 379–387.

    Article  PubMed  CAS  Google Scholar 

  29. Miller, D.M., and Aust, S.D. (1989)Arch. Biochem. Biophys. 271, 113–119.

    Article  PubMed  CAS  Google Scholar 

  30. Jialal I., and Grundy, S.M. (1991)J. Clin. Invest. 87, 597–601.

    Article  PubMed  CAS  Google Scholar 

  31. McCay, P.B. (1985)Ann. Rev. Nutr. 5, 323–340.

    Article  CAS  Google Scholar 

  32. Takahashi, M., Tsuchiya, J., Niki, E., and Urano, S. (1988)J. Nutr. Sci. Vitaminol. 34, 25–34.

    PubMed  CAS  Google Scholar 

  33. Grisar, J.M., Petty, M.A., Bolkenius, F.N., Dow, J., Wagner, J., Wagner, E.R., Haegele, K.D., and DeJong, W. (1991)J. Med. Chem. 34, 257–260.

    Article  PubMed  CAS  Google Scholar 

  34. Pryor, W.A., Kaufman, M.J., and Church, D.F. (1985)J. Am. Chem. Soc. 50, 281–283.

    CAS  Google Scholar 

  35. Kagan, V.E., Serbinova, E.A., and Packer, L. (1990)Arch. Biochem. Biophys. 280, 33–39.

    Article  PubMed  CAS  Google Scholar 

  36. Niki, E., Saito, T., Kawakami, A., and Kamiya, Y. (1984)J. Biol. Chem. 259, 4177–4182.

    PubMed  CAS  Google Scholar 

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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

Authors
  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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