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Lipid peroxidation of isolated chylomicrons and oxidative status in plasma after intake of highly purified eicosapentaenoic or docosahexaenoic acids

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Lipids

Abstract

Fourteen healthy male volunteers were given two separate high-saturated-fat meals with and without the addition of 4 g highly purified ethyl esters of either eicosapentaenoic acid (EPA) (95% pure, n=7) or docosahexaenoic acid (DHA) (90% pure, n=7) supplied as 1-g capsules each containing 3.4 mg vitamin F. The chylomicrons were isolated 6 h after the meals, at peak concentrations of n−3 fatty acids (FA). Addition of n−3 FA with the meal caused a 10.4-fold increase in the concentration of n−3 FA in chylomicrons compared to the saturated fat meal without addition of n−3 FA. After the saturated-fat meal, the concentration of thiobarbituric acid-reactive substances (TBARS) was 327.6±34.6 nmol/mmol triacylglycerol (TAG), which increased to 1015.8±212.0 nmol/mmol TAG (P<0.0001, n=14) after EPA and DHA were added to the meal. There was no significant correlation between the concentrations of TBARS and vitamin E in the chylomicrons collected 6 h after the test meal. The present findings demonstrate an immediate increase in chylomicron peroxidation ex vivo provided by intake of highly purified n−3 FA. The capsular content of vitamin E was absorbed into chylomicrons, but the amount of vitamin E was apparently not sufficient to protect chylomicrons against lipid peroxidation ex vivo. Daily intake of 4 g n−3 FA either as EPA or DHA for 5 wk did not change the plasma concentration of TBARS. Although not significantly different between groups, DHA supplementation decreased total glutathione in plasma (P<0.05) and EPA supplementation increased plasma concentration of vitamin E (P<0.05). The other lipid-soluble and polar antioxidants in plasma remained unchanged during 5 wk of intervention with highly purified n−3 FA.

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Abbreviations

AUC:

area under the curve

CM:

chylomicrons

DHA:

docosahexaenoic acid

EPA:

cicosapentaenoic acid

FA:

fatty acid(s)

HPLC:

high-performance liquid chromatography

LDL:

low density lipoprotein

TAG:

uiacylglycerol

TBA:

thiobarbituric acid

TBARS:

TBA-reactive substance

References

  1. Schmidt, E.B., and Dyerberg, J. (1994) Omega-3 Fatty Acids: Current Status in Cardiovascular Medicine, Drugs 47, 405–424.

    Article  PubMed  CAS  Google Scholar 

  2. Hansen, J.B., Lyngmo, V., Svensson, B., and Nordøy, A. (1993) Inhibition of Exercise-Induced Shortening of Bleeding Time by Fish Oil in Familial Hypercholesterolemia (type IIa), Arterioscl. Thromb. 13, 98–104.

    PubMed  CAS  Google Scholar 

  3. Ross, R. (1993) The Pathogenesis of Atherosclerosis: A Perspective for the 1990s, Nature 362, 801–809.

    Article  PubMed  CAS  Google Scholar 

  4. Cubulsky, M.I., and Gimbrone, M.A., Jr. (1991) Endothelial Expression of Mononuclear Leukocyte Adhesion Molecule During Atherogenesis, Science 251, 788–791.

    Article  Google Scholar 

  5. Kume, N., Cubulsky, M.I., and Gimbrone, M.A., Jr. (1992) Lysophosphatidylcholine, a Component of Atherogenic Lipoproteins, Induces Mononuclear Leukocyte Adhesion Molecules in Cultured Human and Rabbit Arterial Endothelial Cells, J. Clin. Invest. 90, 1138–1144.

    Article  PubMed  CAS  Google Scholar 

  6. Murugesan, G., Chisolm, G.M., and Fox, P.L. (1993) Oxidized Low Density Lipoprotein Inhibits the Migration of Aortic Endothelial Cells in vitro, J. Cell. Biol. 120, 1011–1019.

    Article  PubMed  CAS  Google Scholar 

  7. Witztum, J.L., and Steinberg, D. (1992) Role of Oxidized Low Density Lipoprotein in Atherogenesis, J. Clin. Invest. 88, 1785–1792.

    Google Scholar 

  8. Lougheed, M., Zhang, H., and Steinbrecher, U. (1991) Oxidized Low Density Lipoprotein Is Resistant to Cathepsins and Accumulates Within Macrophages, J. Biol. Chem. 266, 14519–14525.

    PubMed  CAS  Google Scholar 

  9. Holland, J.A., Pritchard, K.A., Rogers, W.J., and Stemerman, M.B. (1988) Perturbation of Cultured Human Endothelial Cells by Atherogenic Levels of Low Density Lipoprotein, Am. J. Pathol. 132, 474–478.

    PubMed  CAS  Google Scholar 

  10. Ku, G., Thomas, C.A., Akeson, A.L., and Jackson, R.L. (1992) Induction of Interleukin 1 Beta Expression from Human Peripheral Blood Monocyte-Derived Macrophages by 9-Hydroxyoctadecadienoic Acid, J. Biol. Chem. 267, 14183–14188.

    PubMed  CAS  Google Scholar 

  11. Harats, D., Dabach, Y., Hollander, G., Ben-Naim, M., Schwartz, R., Berry, E.M., Stein, O., and Stein, Y. (1991) Fish Oil Ingestion in Smokers and Nonsmokers Enhances Peroxidation of Plasma Lipoproteins, Atherosclerosis 90, 127–139.

    Article  PubMed  CAS  Google Scholar 

  12. Nenseter, M.S., Rustan, A.C., Lund-Katz, S., Søyland, E., Mælandsmo, G., Philips, M., and Drevon, C.A. (1992) Effect of Dietary Supplementation with n−3 Polyunsaturated Fatty Acids on Physical Properties and Metabolism of Low Density Lipoproteins in Humans, Arterioscler. Thromb. 12, 369–379.

    PubMed  CAS  Google Scholar 

  13. Bittolo-Bon, G., Cazzolato, G., Alessandrini, P., Soldan, S., Casalino, G., and Avogaro, P. (1993) Effects of Concentrated DHA and EPA Supplementation on LDL Peroxidation and Vitamin E Status in Type IIB Hyperlipemic Patients, in Omega-3 Fatty Acids: Metabolism and Biological Effects (Drevon, C.A., Baksaas, I., and Krokan, H.E., eds.) pp 51–58, Birkhäuser Verlag, Basel.

    Google Scholar 

  14. Zilversmit, D.B. (1979) Atherogenesis: A Postprandial Phenomenon, Circulation 60, 473–485.

    PubMed  CAS  Google Scholar 

  15. Simons, L.A., Dwyer, T., Simons, J., Bernstein, L., Moc, K.P., Poonia, N.S., Balasubramaniam, S., Baron, D., Branson, J., Morgan, J., and Roy, P. (1987) Chylomicrons and Chylomicronremnants in Coronary Artery Disease: A Case-Control Study, Atherosclerosis 65, 181–189.

    Article  PubMed  CAS  Google Scholar 

  16. Patsch, J.R., Miesenböck, G., Hopferwieser, T., Mühlenberger, V., Knapp, E., Dunn, J.K., Gotto, A.M. Jr., and Patsch, W. (1992) Relation of Triglyceride Metabolism and Coronary Artery Disease: Studies in the Postprandial State, Arterioscler. Thromb. 12, 1336–1345.

    PubMed  CAS  Google Scholar 

  17. Staprans, I., Rapp, J.H., Pan, X.M., Kim, K.Y., and Feingold, K.R. (1994) Oxidized Lipids in the Diet Are a Source of Oxidized Lipid in Chylomicrons of Human Serum, Arterioscler. Thromb. 14, 1900–1905.

    PubMed  CAS  Google Scholar 

  18. Weintraub, M.S., Zechner, R., Brown, A., Eisenberg, S., and Breslow, J.L. (1988) Dietary Polyunsaturated Fats of the ω-6 and ω-3 Series Reduce Postprandial Lipoprotein Levels, J. Clin. Invest. 82, 1884–1893.

    PubMed  CAS  Google Scholar 

  19. Harris, W.S., Connor, W.E., Alam, N., and Illingworth, D.R. (1988) Reduction of Postprandial Triglyceridemia in Humans by Dietary n−3 Fatty Acids, J. Lipid Res. 29, 1451–1460.

    PubMed  CAS  Google Scholar 

  20. Grimsgaard, S., Bønaa, K.H., Hansen, J.B., and Nordøy, A. (1997) Highly Purified Eicosapentaenoic Acid and Docosahexaenoic Acid in Humans Have Similar Triacylglycerol-Lowering Effects but Divergent Effects in Serum Fatty Acids, Am. J. Clin. Nutr. 66, 649–659.

    PubMed  CAS  Google Scholar 

  21. Aviram, M., Brox, J., and Nordøy, A. (1986) Effects of Post-prandial Plasma and Chylomicrons on Endothelial Cells, Acta Med. Scand. 219, 341–348.

    Article  PubMed  CAS  Google Scholar 

  22. Folch, J., Lees, M., and Stanley, S. (1957) A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissue, J. Biol. Chem. 226, 497–509.

    PubMed  CAS  Google Scholar 

  23. Hansen, J.B., Grimsgaard, S., Nilsen, H., Nordøy, A., and Bønaa, K.H. (1998) Effects of Highly Purified Eicosapentaenoic Acid and Docosahexaenoic Acid on Fatty Acid Absorption, Incorporation into Serum Phospholipids and Postprandial Triglyceridemia, Lipids 33, 131–138.

    Article  PubMed  CAS  Google Scholar 

  24. Yagi, K. (1976) A Simple Fluorometric Assay for Lipoperoxide in Blood Plasma, Biochem. Med. 15, 212–216.

    Article  PubMed  CAS  Google Scholar 

  25. Ohkawa, H., Ohishi, N., and Yagi, K. (1979) Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Reaction, Anal. Biochem. 95, 351–358.

    Article  PubMed  CAS  Google Scholar 

  26. Demoz, A., Aseidu, D.K., Lie, Ø., and Berge, R.K. (1994) Modulation of Plasma and Hepatic Oxidative Status and Changes in Plasma Lipid Profile by n−3 (EPA and DHA), n−6 (corn oil) and 3-Thia Fatty Acid in Rats, Biochim. Biophys. Acta 1199, 238–244.

    PubMed  CAS  Google Scholar 

  27. Seta, K., Nakamura, H., and Okuyama, T. (1990) Determination of α-Tocopherol, Free Cholesterol, Esterified Cholesterol and Triacylglycerols in Human Lipoproteins by High-Performance Liquid Chromatography, J. Chromatogr. 515, 585–595.

    Article  PubMed  CAS  Google Scholar 

  28. Arnaud, J., Fortis, I., Blachier, S., Kia, D., and Favier, A. (1991) Simultaneous Determination of Retinol, α-Tocopherol and β-Carotene In Serum by Isocratic High-Performance Liquid Chromatography, J. Chromatogr. 572, 103–116.

    PubMed  CAS  Google Scholar 

  29. Sierra, C., Pastor, M.C., and de Ramon, M. (1992) Liquid Chromatography Determination of α-Tocopherol in Erythrocytes, Clin. Chim. Acta 208, 119–126.

    Article  PubMed  CAS  Google Scholar 

  30. Svardal, A.M., Mansoor, M.A., and Ueland, P.M. (1990) Determination of Reduced. Oxidized, and Protein-Bound Glutathione in Human Plasma with Precolumn Derivatization with Monobromobimane and Liquid Chromatography, Anal. Biochem. 184, 338–346.

    Article  PubMed  CAS  Google Scholar 

  31. SAS Institute, Inc: SAS/STAT Guide for Personal Computers, version 6. edn., SAS Institute 1987/1990, Cary.

  32. Mabile, L., Salvayre, R., Bonnate, M.J., and Negre-Salvayre, A. (1995) Oxidizability and Subsequent Cytotoxicity of Chylomicrons to Monocytic U937 and Endothelial Cells Are Dependent on Dietary Fatty Acid Composition, Free Radical Biol. Med. 19, 599–607.

    Article  CAS  Google Scholar 

  33. Drevon, C.A. (1991) Absorption, Transport and Metabolism of Vitamin E, Free Radical Res. Commun. 14, 229–246.

    CAS  Google Scholar 

  34. Kontush, A., Meyer, S., Finckh, B., Kohlschutter, A., and Beisiegel, U. (1996) Alpha-Tocopherol as a Reductant for Cu(II) in Human Lipoproteins. Triggering Role in the Initiation of Lipoprotein Oxidation, J. Biol. Chem. 271, 11106–11112.

    Article  PubMed  CAS  Google Scholar 

  35. Kurtel, H., Liao, L., Grisham, M.B., Tso, P., Aw, T.Y., Anderson, D.C., Miyasaka, M., and Granger, D.N. (1995) Mechanisms of Oxidized Chylomicron-Induced Leukocyte-Endothelial Cell Adhesion, Am. J. Physiol. 268, H2175-H2182.

    PubMed  CAS  Google Scholar 

  36. Demoz, A., Willumsen, N., and Berge, R.K. (1993) Eicosapentaenoic Acid at Hypotriglyceridemic Dose Enhances the Hepatic Antioxidant Defence in Mice, Lipids 27, 968–971.

    Google Scholar 

  37. Calzada, C., Vericel, E., and Lagarde, M. (1992) Lower Levels of Lipid Peroxidation in Human Platelets Incubated with Eicosapentaenoic Acid, Biochim. Biophys. Acta 1127, 147–152.

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine Institute of Clinical Medicine, University of Tromsø, N-9037, Tromsø, Norway

    John-Bjarne Hansen & Arne Nordøy

  2. Department of Medicine Institute of Community Medicine, University of Tromsø, N-9037, Tromsø, Norway

    Kaare H. Bønaa

  3. Laboratory of Clinical Biochemistry, University of Bergen, Bergen, Norway

    Rolf K. Berge

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  1. John-Bjarne Hansen
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  2. Rolf K. Berge
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  4. Kaare H. Bønaa
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Correspondence to John-Bjarne Hansen.

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Hansen, JB., Berge, R.K., Nordøy, A. et al. Lipid peroxidation of isolated chylomicrons and oxidative status in plasma after intake of highly purified eicosapentaenoic or docosahexaenoic acids. Lipids 33, 1123–1129 (1998). https://doi.org/10.1007/s11745-998-0314-7

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  • DOI: https://doi.org/10.1007/s11745-998-0314-7

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