Abstract
It was of interest to investigate the influence of both high doses of eicosapentaenoic acid (EPA) and low doses of 2-or 3-methylated EPA on the antioxidant status, as they all cause hypolipidemia, but the dose required is quite different. We fed low doses (250 mg/d/kg body wt) of different EPA derivatives or high doses (1500 mg/d/kg body wt) of EPA and DHA to rats for 5 and 7 d, respectively. The most potent hypolipidemic EPA derivative, 2,2-dimethyl-EPA, did not change the malondialdehyde content in liver or plasma. Plasma vitamin E decreased only after supplementation of those EPA derivatives that caused the greatest increase in the fatty acyl-CoA oxidase activity. Fatty acyl-CoA oxidase activity increased after administration of both EPA and DHA at high doses. High doses of EPA and DHA decreased plasma vitamin E content, whereas only DHA elevated lipid peroxidation. In liver, however, both EPA and DHA increased lipid peroxidation, but the hepatic level of vitamin E was unchanged. The glutathione-requiring enzymes and the glutathione level were unaffected, and no significant changes in the activities of xanthine oxidase and superoxide dismutase were observed in either low-or high-dose experiments. In conclusion, increased peroxisomal β-oxidation in combination with high amounts of polyunsaturated fatty acids caused elevated lipid peroxidation. At low doses of polyunsaturated fatty acids, lipid peroxidation was unchanged, in spite of increased peroxisomal β-oxidation, indicating that polyunsaturation is the most important factor for lipid peroxidation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- DHA:
-
docosahexaenoic acid
- EPA:
-
eicosapentaenoic acid
- FAO:
-
fatty acyl-CoA oxidase
- HPLC:
-
high-performance liquid chromatography
- MDA:
-
malondialdehyde
- PUFA:
-
polyunsaturated fatty acid
- SOD:
-
superoxide dismutase
- XDH:
-
xanthine dehydrogenase
- XOX:
-
xanthine oxidase
References
Reddy, J.K., and Lalwani, N.D. (1983) Carcinogenesis by Hepatic Peroxisome Proliferators: Evaluation of the Risk of Hypolipidemic Drugs and Industrial Plasticizers to Humans, Crit. Rev. Toxicol. 12, 1–58.
Barzanti, V., Pregnolato, P., Maranesi, M., Bosi, I., Baracca, A., Solaini, G., and Turchetto, E. (1995) Effects of Dietary Oils Containing Graded Amounts of 18∶3n−6 and 18∶4n−3 on Cell Plasma Membranes Nutr. Biochem. 6, 21–26.
Garrido, A., Garrido, F., Guerra, R., and Valenzuela, A. (1989) Ingestion of High Doses of Fish Oil Increases the Susceptibility of Cellular Membranes to the Induction of Oxidative Stress, Lipids 24, 833–835.
Mouri, K., Ikesu, H., Esaka, T., and Igarashi, O. (1984) The Influence of Marine Oil Intake Upon Levels of Lipids, α-Tocopherol and Lipid Peroxidation in Serum and Liver of Rats, J. Nutr. Sci. Vitaminol. 30, 307–318.
Witting, L.A., and Horwitt, M.K. (1964) Effect of Degree of Fatty Acid Unsaturation in Tocopherol Deficiency-Induced Creatinuria, J. Nutr. 82, 19–33.
Demoz, A., Asiedu, 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 a 3-Thia Fatty Acid in Rats, Biochim. Biophys. Acta 1199, 238–244.
Willumsen, N., Hexeberg, S., Skorve, J., Lundquist, M., and Berge, R.K. (1993) Docosahexaenoic Acid Shows No Triglyceride-Lowering Effects but Increases the Peroxisomal Fatty Acid Oxidation in Liver of Rats, J. Lipid Res. 34, 13–22.
Berge, R.K., Flatmark, T., and Osmundsen, H. (1984) Enhancement of Long-Chain Acyl-CoA Hydrolase Activity in Peroxisomes and Mitochondria of Rat Liver by Peroxisomal Proliferators, Eur. J. Biochem. 141, 637–644.
Halliwell, B., and Chirico, S. (1993) Lipid Peroxidation: Its Mechanism, Measurement, and Significance, Am. J. Clin. Nutr. 57 (suppl), 715S-725S.
Bolann, B.J., and Ulvik, R.J. (1991) Improvement of a Direct Spectrophotometric Assay for Routine Determination of Superoxide Dismutase Activity, Clin. Chem. 37, 1993–1999.
Small, G.M., Burdett, K., and Connock, M.J. (1985) A Sensitive Spectrophotometric Assay for Peroxisomal Acyl-CoA Oxidase, Biochem. J. 227, 205–210.
Feinberg, A.P., and Vogelstein, B. (1984) ADDENUM A Technique for Radiolabelling DNA Restriction Endonuclease Fragments to High Specific Activity, Anal. Biochem. 137, 266–267.
Lai, C.-C., Huang, W.-H., Askari, A., Wang, Y., Sarvazyan, N., Klevay, L.M., and Chiu, T.H. (1994) Differential Regulation of Superoxide Dismutase in Copper-Deficient Rat Organs, Free Radical Biol. Med. 16, 613–620.
Chomczynski, P., and Sacchi, N. (1987) Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction, Anal. Biochem. 162, 156–159.
Aasland, R., Lillehaug, J.R., Male, R., Jøsendal, O., Varhaug, J.E., and Kleppe, K. (1988) Expression of Oncogenes in Thyroid Tumours: Coexpression of c-erbB2/neu and c-erbB, Br. J. Cancer 57, 358–363.
Sambrook, J., Fritsch, E., and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual, 2nd edn., Cold Spring Harbor Laboratory Press, New York.
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.
Willumsen, N., Skorve, J., Hexeberg, S., Rustan, A.C., and Berge, R.K. (1993) The Hypotriglyceridemic Effect of Eicosapentaenoic Acid in Rats Is Reflected in Increased Mitochondrial Fatty Acid Oxidation Followed by Diminished Lipogenesis, Lipids 28, 683–690.
Calviello, G., Palozza, P., Franceschelli, P., and Bartoli, G.M. (1997) Low-Dose Eicosapentaenoic or Docosahexaenoic Acid Administration Modifies Fatty Acid Composition and Does Not Affect Susceptibility to Oxidative Stress in Rat Erythrocytes and Tissues, Lipids 32, 1075–1083.
Frøyland, L., Madsen, L., Vaagenes, H., Totland, G.K., Auwerx, J., Kryvi, H., Staels, B., and Berge, R.K. (1997) Mitochondrion Is the Principal Target for Nutritional and Pharmacological Control of Triglyceride Metabolism, J. Lipid Res. 38, 1851–1858.
Madsen, L., Frøyland, L., Dyrøy, E., Helland, K., and Berge, R.K. (1998) Docosahexaenoic Acid and Eicosapentaenoic Acids Are Differently Metabolized in Rat Liver During Mitochondria and Peroxisome Proliferation, J. Lipid Res. 39, 583–593.
Drevon, C.A. (1991) Absorption, Transport and Metabolism of Vitamin E, Free Radical Res. Commun. 14, 229–246.
Reaven, P. (1996) The Role of Dietary Fat in LDL Oxidation and Atherosclerosis, Nutr. Metab. Cardiovasc. Dis. 6, 57–64.
Glueck, C.J., Shaw, P., Lang, J.E., Tracy, T., Sieve-Smith, L., and Wang, Y. (1995) Evidence That Homocysteine Is an Independent Risk Factor for Atherosclerosis in Hypolipidemic Patients, Am. J. Cardiol. 75, 132–136.
Blom, H.J., Kleinveld, H.A., Boers, G.H., Demacker, P.N., Hak-Lemmers, H.L., Te-Poele-Pothoff, M.T., and Trijbels, J.M. (1995) Lipid Peroxidation and Susceptibility of Low-Density Lipoprotein to in vitro Oxidation in Hyperhomocysteinaemia, Eur. J. Clin. Invest. 25, 149–154.
Halvorsen, B., Brude, I., Drevon, A.C., Nysom, J., Ose, L., Christiansen, E.N., and Nenseter, M.S. (1996) Effect of Homocysteine on Copper Ion-Catalyzed, Azo Compound-Initiated, and Mononuclear Cell-Mediated Oxidative Modification of Low Density Lipoprotein, J. Lipid Res. 37, 1591–1600.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Vaagenes, H., Muna, Z.A., Madsen, L. et al. Low doses of eicosapentaenoic acid, docosahexaenoic acid, and hypolipidemic eicosapentaenoic acid derivatives have no effect on lipid peroxidation in plasma. Lipids 33, 1131–1137 (1998). https://doi.org/10.1007/s11745-998-0315-6
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11745-998-0315-6