Skip to main content
SpringerLink
Log in

Levels of Lipid Peroxidation in Human Plasma and Erythrocytes: Comparison between Fatty Acids and Cholesterol

  • Original Article
  • Published:
Lipids

Abstract

Lipid peroxidation has gained renewed attention with increasing evidence showing its biological role in producing toxic compounds and cellular signaling mediators. The assessment of lipid peroxidation levels in vivo is difficult partly because lipids are oxidized by different oxidants by different mechanisms to give versatile types of products, which may undergo metabolism and secondary reactions. In the present study, total hydroxyoctadecadienoic acids (tHODE) and 7α- and 7β-hydroxycholesterol (t7-OHCh) from 44 healthy human subjects were assessed as biomarkers after reduction with sodium borohydride followed by saponification with potassium hydroxide comparing with the prevailing standard 8-isoprostaglandin F2α (t8-iso-PGF2α). The average concentrations of tHODE, total 8-isoprostaglandin F2α (t8-iso-PGF2α), t7α-OHCh, and t7β-OHCh were 203, 0.727, 87.1, and 156 nmol/l plasma and 1,917, 12.8, 1,372, and 3,854 nmol/l packed erythrocytes, respectively. The ratios of tHODE and t7-OHCh to the parent substrates were 194 and 3,519 μmol tHODE/mol linoleates and 40.9 and 686 μmol t7-OHCh/mol cholesterol in plasma and erythrocytes, respectively. It was found that (1) t7-OHCh in blood was unexpectedly high, as high as or even higher than tHODE, (2) the amounts of tHODE was more than 100 fold higher than t8-iso-PGF2α (3) the level of lipid oxidation products in erythrocytes was higher than that in plasma, and (4) lipid peroxidation products level tended to increase while antioxidant level decrease with age. These products may be used as potential biomarker for assessment of lipid peroxidation and oxidative stress in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

BHT:

2, 6-Di-tert-butyl-4-methylphenol

BOSS:

Biomarkers of oxidative stress study

BSTFA:

N,O-Bis(trimethylsilyl)trifluoroacetamide

CoQ10:

Coenzyme Q10 (ubiquinol-10 + ubiquinone-10);

HV:

Hematocrit value

9-HODE-d4 :

9S-Hydroxy-10E, 12Z-octadecadienoic-9,10,12,13-d4 acid

HPODE:

Hydroperoxyoctadecadienoic acid

t8-iso-PGF2α :

Total 8-iso-prostaglandin F2α

8-iso-PGF2α-d4 :

8-Iso-prostaglandin F2α-d4;

7-KCh:

7-Ketocholesterol

LDL:

Low density lipoprotein

PBS:

Phosphate-buffered saline

SeP:

Selenoprotein P

tCh:

Total cholesterol

7-OOHCh:

7-Hydroperoxycholesterol

t7-OHCh:

Total 7-hydroxycholesterol

t18:2:

Total linoleate

tHODE:

Total hydroxyoctadecadienoic acid

Q10H2 :

Ubiquinol-10

Q10 :

Ubiquinone-10

αT:

α-Tocopherol

ZE/EE :

Stereoisomer ratio of HODE (9- and 13-(Z,E)-HODE/9- and 13-(E,E)-HODE)

References

  1. Niki E, Yoshida Y, Saito Y, Noguchi N (2005) Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun 338:668–676

    Article  PubMed  CAS  Google Scholar 

  2. Leonarduzzi G, Arkan MC, Basaga H, Chiarpotto E, Sevanian A, Poli G (2000) Lipid oxidation products in cell signaling. Free Rad Biol Med 28:1370–1378

    Article  PubMed  CAS  Google Scholar 

  3. Ceaser EK, Moellering DR, Shiva S, Ramachandran A, Landar A, Venkartraman A, Crawford J, Patel R, Dickinson DA, Ulasova E, Ji S, Darley-Usmar VM (2004) Mechanisms of signal transduction mediated by oxidized lipids: the role of the electrophile-responsive proteome. Biochem Soc Trans 32:151–155

    Article  PubMed  CAS  Google Scholar 

  4. Chen ZH, Saito Y, Yoshida Y, Sekine A, Noguchi N, Niki E (2005) 4-Hydroxynonenal induces adaptive response and enhances PC12 celltolerance primarily through induction of thioredoxin reductase 1 via activation of Nrf2. J Biol Chem 51:41921–41927

    Article  Google Scholar 

  5. Chen ZH, Yoshida Y, Saito Y, Sekine A, Noguchi N, Niki E (2006) Induction of adaptive response and enhancement of PC12 cell tolerance by 7-hydroxycholesterol and 15-deoxy-delta-prostaglandin J2 through up-regulation of cellular glutathione by different mechanisms. J Biol Chem 281:14440–14445

    Article  PubMed  CAS  Google Scholar 

  6. Gao L, Wang J, Sekhar KR, Yin H, Yared NF, Schneider SN, Sasi S, Dalton TP, Anderson ME, Chan JY, Morrow JD, Freeman ML (2007) Novel N-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between keap1 and cullin3. J Biol Chem 282:2529–2537

    Article  PubMed  CAS  Google Scholar 

  7. Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ II (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 87:9383–9387

    Article  PubMed  CAS  Google Scholar 

  8. Musiek ES, Yin H, Milne GL, Morrow JD (2005) Recent advances in the biochemistry and clinical relevance of the isoprostane pathway. Lipids 40:987–994

    Article  PubMed  CAS  Google Scholar 

  9. Yoshida Y, Niki E (2004) Detection of lipid peroxidation in vivo: total hydroxyoctadecadienoic acid and 7-hydroxycholesterol as oxidative stress marker. Free Rad Res 38:787–794

    Article  CAS  Google Scholar 

  10. Porter NA, Caldwell SE, Mills KA (1995) Mechanisms of free radical oxidation of unsaturated lipids. Lipids 30:277–290

    Article  PubMed  CAS  Google Scholar 

  11. Pikuleva IA (2006) Cholesterol-metabolizing cytochromes P450. Drug Metab Dispos 34:513–520

    Article  PubMed  CAS  Google Scholar 

  12. Smith LL, Johnson BH (1989) Biological activies of oxysterols. Free Rad Biol Med 7:285–332

    Article  PubMed  CAS  Google Scholar 

  13. Saito Y, Watanabe Y, Saito E, Honjoh T, Takahashi K (2001) Production and application of monoclonal antibodies to human selenoprotein P. J Health Sci 47:346–352

    Article  CAS  Google Scholar 

  14. Barclay LRC, Vinqvist MR, Antunes F, Pinto RE (1997) Antioxidant activity of vitamin E determined in a phospholipid membrane by product studies: avoiding chain transfer reactions by vitamin E radicals. J Am Chem Soc 119:5764–5765

    Article  CAS  Google Scholar 

  15. Noguchi N, Numano R, Kaneda H, Niki E (1998) Oxidation of lipids in low density lipoprotein particles. Free Rad Res 29:43–52

    Article  CAS  Google Scholar 

  16. Sevanian A, Seraglia R, Traldi P, Rossato P, Ursini F, Hodis H (1994) Analysis of plasma cholesterol oxidation products using gas- and high-performance liquid chromatography/mass spectrometry. Free Rad Biol Med 17:397–409

    Article  PubMed  CAS  Google Scholar 

  17. Brown AJ, Jessup W (1999) Oxysterols and atherosclerosis. Atherosclerosis 142:1–28

    Article  PubMed  CAS  Google Scholar 

  18. Diczfalusy U (2004) Analysis of cholesterol oxidation products in biological samples. J AOAC Int 87:467–473

    PubMed  CAS  Google Scholar 

  19. BjÖkhem I, Reihner E, Angelin B, Ewerth S, Akerlund JE, Einarsson K (1987) On the possible use of the serum level of 7α-hydroxycholesterol as a marker for increased activity of the cholesterol 7α-hydroxylase in humans. J Lipid Res 28:889–894

    Google Scholar 

  20. Schweizer RA, Zurcher M, Balazs Z, Dick B, Odermatt A (2004) Rapid hepatic metabolism of 7-ketocholesterol by 11 beta-hydroxysteroid dehydrogenase type 1: species-specific differences between the rat, human, and hamster enzyme. J Biol Chem 279:18415–18424

    Article  PubMed  CAS  Google Scholar 

  21. Hult M, Elleby B, Shafqat N, Svensson S, Rane A, Jornvall H, Abrahmsen L, Oppermann U (2004) Human and rodent type 11 beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. Cell Mol Life Sci 61:992–999

    Article  PubMed  CAS  Google Scholar 

  22. Arampatzis S, Kadereit B, Schuster D, Balazs Z, Schweizer RA, Frey FJ, Langer T, Odermatt A (2005) Comparative enzymology of 11 beta-hydroxysteroid dehydrogenase type 1 from six species. J Mol Endocrinol 35:89–101

    Article  PubMed  CAS  Google Scholar 

  23. Thomas JP, Maiorino M, Ursini F, Girotti AW (1990) Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. J Biol Chem 265:454–461

    PubMed  CAS  Google Scholar 

  24. Kühn H, Borchert A (2002) Regulation of enzymatic lipid peroxidation: the interplay of peroxidation and peroxide reducing enzymes. Free Rad Biol Med 33:154–172

    Article  PubMed  Google Scholar 

  25. Kühn H, Heydeck D, Hugou I, Gniwotta C (1997) In vivo action of 15-lipoxygenase in early stages of human atherogenesis. J Clin Invest 99:888–893

    Article  PubMed  Google Scholar 

  26. Yamashita H, Nakamura A, Noguchi N, Niki E, Kühn H (1999) Oxidation of low density lipoprotein and plasma by 15-lipoxygenase and free radicals. FEBS Lett 445:287–290

    Article  PubMed  CAS  Google Scholar 

  27. Dufour C, Loonis M (2005) Regio- and stereoselective oxidation of linoleic acid bound to serum albumin: identification by ESI-mass spectrometry and NMR of the oxidation products. Chem Phys Lipids 138:60–68

    Article  PubMed  CAS  Google Scholar 

  28. Niki E, Yamamoto Y, Takahashi M, Yamamoto K, Yamamoto Y, Komuro E, Miki M, Yasuda H, Mino M (1988) Free-radical mediated damage of blood and its inhibition by antioxidants. J Nutr Sci Vitaminol 34:507–512

    PubMed  CAS  Google Scholar 

  29. Kadiiska MB, Gladen BC, Baird DD, Germolec D, Graham LB, Parker CE, Nyska A, Wachsman JT, Ames BN, Basu S, Brod N, FitzGerald GA, Floyd RA, George M, Heinecke JW, Hatch GE, Hensley K, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts II LJ, Rokach J, Shigenaga MK, Sohal RS, Sun J, Tice RR, Van Thiel DH, Wellner D, Walter PB, Tomer KB, Mason RP, Barrett JC (2005) Biomarkers of oxidative stress study II. Are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Rad Biol Med 38:698–710

    Article  PubMed  CAS  Google Scholar 

  30. Kadiiska MB, Gladen BC, Baird DD, Graham LB, Parker CE, Ames BN, Basu S, FitzGerald GA, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts II LJ, Rokach J, Shigenaga MK, Sun J, Walter PB, Tomer KB, Barrett JC, Mason RP (2005) Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning. Free Rad Biol Med 38:711–718

    Article  PubMed  CAS  Google Scholar 

  31. Yoshida Y, Itoh N, Hayakawa M, Piga R, Cynshi O, Jishage K, Niki E (2005) Lipid peroxidation induced by carbon tetrachloride and its inhibition by antioxidant as evaluated by an oxidative stress marker, HODE. Toxicol Appl Pharmacol 208:87–97

    Article  PubMed  CAS  Google Scholar 

  32. Yoshida Y, Itoh N, Hayakawa M, Habuchi Y, Inoue R, Chen ZH, Cao J, Cynshi O, Niki E (2006) Lipid peroxidation in mice fed choline-deficient diet and its inhibition by antioxidants as evaluated by an oxidative stress marker, HODE. Nutrition 22:303–311

    Article  PubMed  CAS  Google Scholar 

  33. Tanito M, Yoshida Y, Kaidzu S, Ohira A, Niki E (2006) Detection of lipid peroxidation in light-exposed mouse retina assessed by oxidative stress markers, total hydroxyoctadecadienoic acid and 8-iso-prostaglandin F2α. Neurosci Lett 398:63–68

    Article  PubMed  CAS  Google Scholar 

  34. Yoshida Y, Hayakawa M, Niki E (2005) Total hydroxyoctadecadienoic acid as a marker for lipid peroxidation in vivo. BioFactors 24:7–15

    PubMed  CAS  Google Scholar 

  35. Yoshida Y, Hayakawa M, Habuchi Y, Niki E (2006) Evaluation of the dietary effects of coenzyme Q in vivo by the oxidative stress marker, hydroxyoctadecadienoic acid and its stereoisomer ratio. Biochim Biophys Acta 1760:1558–1568

    PubMed  CAS  Google Scholar 

  36. Kitano S, Yoshida Y, Kawano K, Hibi N, Niki E (2007) Oxidative status of human low density lipoprotein isolated by anion-exchange high-performance liquid chromatography—assessment by total hydroxyoctadecadienoic acid, 7-hydroxycholesterol, and 8-iso-prostaglandin F2α. Anal Chim Acta 585:86–93

    Article  PubMed  CAS  Google Scholar 

  37. Kalen A, Appelkvist EL, Dallner G (1989) Age-related changes in the lipid compositions of rat and human tissues. Lipids 24:579–584

    Article  PubMed  CAS  Google Scholar 

  38. Komorowski J, Muratsu K, Nara Y, Willis R, Folkers K (1988) Significance of biological parameters of human blood levels of CoQ10. BioFactors 1:67–69

    PubMed  CAS  Google Scholar 

  39. Zita C, Overvad K, Mortensen SA, Sindberg CD, Moesgaard S, Hunter DA (2003) Serum coenzyme Q10 concentrations in healthy men supplemented with 30 mg or 100 mg coenzyme Q10 for two months in a randomised controlled study. BioFactors 18:185–193

    PubMed  CAS  Google Scholar 

  40. Miles MV, Horn PS, Morrison JA, Tang PH, DeGrauw T, Pesce AJ (2003) Plasma coenzyme Q10 reference intervals, but not redox status, are affected by gender and race in self-reported healthy adults. Clin Chim Acta 332:123–132

    Article  PubMed  CAS  Google Scholar 

  41. Kaikkonen J, Kosonen L, Nyyssonen K, Ristonmaa U, Salonen JT (1998) Effect of combined coenzyme Q10 and d-α-tocopheryl acetate supplementation on exercise-induced lipid peroxidation and muscular damage: a placebo-controlled double-blind study in marathon runners. Free Rad Res 29:85–92

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577, Japan

    Yasukazu Yoshida, Yoshiro Saito, Mieko Hayakawa, Yoko Habuchi & Etsuo Niki

  2. Department of Internal Medicine, Ikeda Municipal Hospital, 3-1-18 Johnan, Ikeda, Osaka, 563-8510, Japan

    Yasuharu Imai & Yoshiyuki Sawai

Authors
  1. Yasukazu Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshiro Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mieko Hayakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoko Habuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuharu Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshiyuki Sawai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Etsuo Niki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasukazu Yoshida.

About this article

Cite this article

Yoshida, Y., Saito, Y., Hayakawa, M. et al. Levels of Lipid Peroxidation in Human Plasma and Erythrocytes: Comparison between Fatty Acids and Cholesterol. Lipids 42, 439–449 (2007). https://doi.org/10.1007/s11745-007-3037-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-007-3037-5

Keywords

Search

Navigation