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Dietary Virgin Olive Oil Reduces Oxidative Stress and Cellular Damage in Rat Brain Slices Subjected to Hypoxia–Reoxygenation

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Lipids

Abstract

We investigated how virgin olive oil (VOO) affected platelet and hypoxic brain damage in rats. Rats were given VOO orally for 30 days at 0.25 or 0.5 mL kg−1 per day (doses A and B, respectively). Platelet aggregation, thromboxane B2, 6-keto-PGF, and nitrites + nitrates were measured, and hypoxic damage was evaluated in a hypoxia–reoxygenation assay with fresh brain slices. Oxidative stress, prostaglandin E 2, nitric oxide pathway activity and lactate dehydrogenase (LDH) activity were also measured. Dose A inhibited platelet aggregation by 36% and thromboxane B2 by 19%; inhibition by dose B was 47 and 23%, respectively. Virgin olive oil inhibited the reoxygenation-induced increase in lipid peroxidation (57% in control rats vs. 2.5% (P < 0.05) in treated rats), and reduced the decrease in glutathione concentration from 67 to 24% (dose A) and 41% (dose B). Brain prostaglandin E 2 after reoxygenation was 306% higher in control animals, but the increases in treated rats were only 53% (dose A) and 45% (dose B). The increases in nitric oxide production (213% in controls) and activity of the inducible isoform of nitric oxide synthase (175% in controls) were both smaller in animals given VOO (dose A 84%; dose B 12%). Lactate dehydrogenase activity was reduced by 17% (dose A) and 42% (dose B). In conclusion, VOO modified processes related to thrombogenesis and brain ischemia. It reduced oxidative stress and modulated the inducible isoform of nitric oxide synthase, diminishing platelet aggregation and protecting the brain from the effects of hypoxia–reoxygenation.

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Abbreviations

cNOS:

Constitutive isoform of nitric oxide synthase

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

GSHpx:

Glutathione peroxidase

GSHtf:

Glutathione transferase

iNOS:

Inducible isoform of nitric oxide synthase

LDH:

Lactate dehydrogenase

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NO2 + NO3 :

Plasma nitrite + nitrate

PGE2 :

Prostaglandin E 2

TxB2 :

Thromboxane B2

TBARS:

Thiobarbituric acid reactive substances

VOO:

Virgin olive oil

References

  1. Barzi F, Woodward M, Marfisi RM, Tavazzi L, Valagussa F, Marchioli R, GISSI-Prevenzione Investigators (2003) Mediterranean diet and all-causes mortality after myocardial infarction: results from the GISSI-Prevenzione trial. Eur J Clin Nutr 57:604–611

    Article  CAS  PubMed  Google Scholar 

  2. de Lorgril M, Salen P, Martin JL, Mamelle N, Monjaud I, Touboul P, Delaye J (1996) Effect of a mediterranean type diet on the rate of cardiovascular complications in patients with coronary artery disease. J Am Coll Cardiol 28:1103–1108

    Article  Google Scholar 

  3. Keys A (1980) Seven countries: a multivariate analysis of diet and coronary heart disease. Harvard University Press, Boston

    Google Scholar 

  4. Knoops KT, Groot de LC, Fidanza F, Alberti-Fidanza A, Kromhout D, van Staveren WA (2006) Comparison of three different dietary scores in relation to 10-year mortality in elderly European subjects: the HALE project. Eur J Clin Nutr 60:746–755

    Article  CAS  PubMed  Google Scholar 

  5. Trichopoulou A, Orfanos P, Norat T, Bueno-de-Mesquita B, Ocke MC, Peeters PH, van der Schouw YT, Boeing H, Hoffmann K et al (2005) Modified mediterranean diet and survival: EPIC-elderly prospective cohort study. BMJ 330:991–998

    Article  PubMed  Google Scholar 

  6. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, Erdman JW Jr, Kris-Etherton P, Goldberg IJ, et al. (2000) AHA dietary guidelines: revision 2000: a statement for healthcare professionals from the nutrition committee of the American heart association. Stroke 31:2751–2766

    CAS  PubMed  Google Scholar 

  7. World Health Organization Study Group (2003) Diet, nutrition, and the prevention of chronic diseases. Geneva, Switzerland. World Health Organization; Technical Report Series 916

  8. McCord JM, Edeas MA (2005) SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed Pharmacother 59:139–142

    Article  CAS  PubMed  Google Scholar 

  9. Violi F, Cangemi R (2005) Antioxidants and cardiovascular disease. Curr Opin Investig Drugs 6:895–900

    CAS  PubMed  Google Scholar 

  10. Visioli F, Poli A, Gall C (2002) Antioxidant and other biological activities of phenols from olives and olive oil. Med Res Rev 22:65–75

    Article  CAS  PubMed  Google Scholar 

  11. Alexandrova ML, Bochev PG (2005) Oxidative stress during the chronic phase after stroke. Free Radic Biol Med 39:297–316

    Article  CAS  PubMed  Google Scholar 

  12. Guix FX, Uribesalgo I, Coma M, Munoz FJ (2005) The physiology and pathophysiology of nitric oxide in the brain. Prog Neurobiol 76:126–152

    Article  CAS  PubMed  Google Scholar 

  13. Weinbrenner T, Fito M, Farre Albaladejo M, Saez GT, Rijken P, Tormos C, Coolen S, De La Torre R, Covas MI (2004) Bioavailability of phenolic compounds from olive oil and oxidative/antioxidant status at postprandial state in healthy humans. Drugs Exp Clin Res 30:207–212

    CAS  PubMed  Google Scholar 

  14. De La Cruz JP, Villalobos MA, Sedeno G, Sanchez De La Cuesta F (1998) Effect of propofol on oxidative stress in an in vitro model of anoxia-reoxygenation in the rat brain. Brain Res 800:136–144

    Article  PubMed  Google Scholar 

  15. Bossman HB, Hemsworth BD (1969) Structure and function of nervous system. Academic, London, pp 1–24

    Google Scholar 

  16. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  17. Hissin PJ, Hill R (1976) A fluorimetric method of determination of oxidized and reduced glutathione in tissues. Anal Biochem 74:214–226

    Article  CAS  PubMed  Google Scholar 

  18. Flohé L, Gunzler WA (1985) Assays of glutathione peroxidase. Meth Enzymol 105:114–121

    Article  Google Scholar 

  19. Warholm M, Guthenberg C, von Bahr C, Mannervik B (1985) Glutathione transferases from human liver. Meth Enzymol 113:449–503

    Google Scholar 

  20. Lobner D (2000) Comparison of the LDH and MTT assays for quantifying cell death: validity for neuronal apoptosis? J Neurosci Meth 96:147–152

    Article  CAS  Google Scholar 

  21. Kelly CM, Smith RD, Williams CM (2001) Dietary monounsaturated fatty acids and haemostasis. Proc Nutr Soc 60:161–170

    CAS  PubMed  Google Scholar 

  22. Freese R, Mutanen M, Valsta LM, Salminen I (1994) Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/alpha-linolenic acid ratio on platelet aggregation. Thromb Haemost 71:73–77

    CAS  PubMed  Google Scholar 

  23. Vicario IM, Malkova D, Lund EK, Johnson IT (1998) Olive oil supplementation in healthy adults: effects in cell membrane fatty acid composition and platelet function. Ann Nutr Metab 42:160–169

    Article  CAS  PubMed  Google Scholar 

  24. Turpeinen AM, Pajari AM, Freese R, Sauer R, Mutanen M (1998) Replacement of dietary saturated by unsaturated fatty acids: effects of platelet protein kinase C activity, urinary content of 2,3-dinor-TXB2 and in vitro platelet aggregation in healthy man. Thromb Haemost 80:649–655

    CAS  PubMed  Google Scholar 

  25. Visioli F, Caruso D, Grande S, Bosisio R, Villa M, Galli G, Sirtori C, Galli C (2005) Eur J Nutr 44:121–127

    Article  CAS  PubMed  Google Scholar 

  26. Bartoli R, Fernandez-Banares F, Navarro E, Castella E, Mane J, Alvarez M, Pastor C, Cabre E, Gassull MA (2000) Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E(2) synthesis. Gut 46:191–199

    Article  CAS  PubMed  Google Scholar 

  27. De La Cruz JP, Villalobos MA, Carmona JA, Martín-Romero M, Sánchez de la Cuesta F (2000) Antithrombotic potential of olive oil administration in rabbits with elevated cholesterol. Thromb Res 100:305–315

    Article  PubMed  Google Scholar 

  28. Moreno JJ (2003) Effect of olive oil minor components on oxidative stress and arachidonic acid mobilization and metabolism by macrophages RAW 264.7. Free Radic Biol Med 35:1073–1081

    Article  CAS  PubMed  Google Scholar 

  29. Nieto N, Torres MI, Ríos A, Gil A (2002) Dietary polyunsaturated fatty acids improve histological and biochemical alterations in rats with experimental ulcerative colitis. J Nutr 132:11–19

    CAS  PubMed  Google Scholar 

  30. Perona JS, Cabello-Moruno R, Ruiz-Gutierrez V (2006) The role of virgin olive oil components in the modulation of endothelial function. J Nutr Biochem 14:429–445

    Article  CAS  Google Scholar 

  31. De La Cruz JP, Quintero L, Villalobos MA, Sánchez de la Cuesta F (2000) Lipid peroxidation and glutathione system in hyperlipemic rabbits: influence of olive oil administration. Biochim Biophys Acta 1485:36–44

    PubMed  Google Scholar 

  32. De La Puerta R, Domínguez ME, Ruíz V, Flavill JA, Hoult JRS (2001) Effects of virgin olive oil on scavenging of reactive nitrogen species and upon nitrergic neurotransmission. Life Sci 69:1213–1222

    Article  Google Scholar 

  33. Villalobos MA, De La Cruz JP, Carrasco T, Smith-Agreda JM, Sanchez de la Cuesta F (1994) Effects of alpha-tocopherol on lipid peroxidation and mitochondrial reduction of tetraphenyl tetrazolium in the rat brain. Brain Res Bull 33:313–318

    Article  CAS  PubMed  Google Scholar 

  34. Visioli F, Bellomo G, Galli C (1998) Free radical-scavenging properties of olive oil polyphenols. Biochem Biophys Res Commun 247:60–64

    Article  CAS  PubMed  Google Scholar 

  35. De La Cruz JP, Martin-Romero M, Carmona JA, Villalobos MA, Sanchez de la Cuesta F (1997) Effect of evening primrose oil on platelet aggregation in rabbits fed an atherogenic diet. Thromb Res 87:141–149

    Article  PubMed  Google Scholar 

  36. Hünkar T, Aktan F, Ceylan A, Karasu Ç (2002) Effects of cod liver oil on tissue antioxidant pathways in normal and streptozotocin-diabetic rats. Cell Biochem Funct 20:297–302

    Article  PubMed  CAS  Google Scholar 

  37. López-Torres M, Thiele JJ, Sindo Y, Han D, Packer L (1998) Topical application of n-tocopherol modulates the antioxidant network and diminishes ultraviolet-induced oxidative damage in murine skin. Br J Dermatol 138:207–215

    Article  PubMed  Google Scholar 

  38. Ochoa-Herrera JJ, Huertas JR, Quiles JL, Mataix J (2001) Dietary oils high in oleic acid, but with different non-glyceride contents, have different effects on lipid profiles and peroxidation in rabbit hepatic mitochondria. J Nutr Biochem 12:357–364

    Article  CAS  PubMed  Google Scholar 

  39. O´Bannion MK (1999) cyclooxygenase-2 and Alzheimer’s disease: potential roles in inflammation and neurodegeneration. Expert Opin Investig Drugs 8:1521–1536

    Article  Google Scholar 

  40. Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Alvarez D, Al-Dalain S, Martinez G, Leon OS, Springer JE (2003) Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia. J Neurochem 86:545–555

    Article  CAS  PubMed  Google Scholar 

  41. Pepicelli O, Fedele E, Berardi M, Raiteri M, Levi G, Greco A, Ajmone-Cat MA, Minghetti L (2005) Cyclo-oxygenase-1 and -2 differently contribute to prostaglandin E2 synthesis and lipid peroxidation after in vivo activation of N-methyl-d-aspartate receptors in rat hippocampus. J Neurochem 93:1561–1567

    Article  CAS  PubMed  Google Scholar 

  42. Schwab JM, Beschorner R, Meyermann R, Gozalan F, Schluesener HJ (2002) Persistent accumulation of cyclooxygenase-1-expressing microglial cells and macrophages and transient upregulation by endothelium in human brain injury. J Neurosurg 96:892–899

    CAS  PubMed  Google Scholar 

  43. Yermakova AV, Rollins J, Callahan LM, Rogers J, O’Banion MK (1999) Cyclooxygenase-1 in human Alzheimer and control brain: quantitative analysis of expression by microglia and CA3 hippocampal neurons. J Neuropathol Exp Neurol 58:1135–1146

    Article  CAS  PubMed  Google Scholar 

  44. Fang YZ, Yang S, Wu G (2002) Free radicals, antioxidants, and nutrition. Nutrition 18:872–879

    Article  CAS  PubMed  Google Scholar 

  45. Deiana M, Aruoma OI, Bianchi ML, Spencer JP, Kaur H, Halliwell B, Aeschbach R, Banni S, Dessi MA, Corongiu FP (1999) Inhibition of peroxynitrite dependent DNA base modification and tyrosine nitration by the extra virgin olive oil-derived antioxidant hydroxytyrosol. Free Radic Biol Med 26:762–769

    Article  CAS  PubMed  Google Scholar 

  46. D’Angelo S, Manna C, Migliardi V, Mazzoni O, Morrica P, Capasso G, Pontoni G, Galletti P, Zappia V (2001) Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil. Drug Metab Dispos 29:1492–1498

    CAS  PubMed  Google Scholar 

  47. Schaffer S, Podstawa M, Visioli F, Bogani P, Müller WE, Eckert GP (2007) Hydroxytyrosol-rich olive mill wastewater protects brain cells in vitro and ex vivo. J Agric Food Chem 55:5043–5049

    Article  CAS  PubMed  Google Scholar 

  48. Martinez-Gonzalez MA (2006) The SUN cohort study (Seguimiento University of Navarra). Public Health Nutr 9:127–131

    Article  PubMed  Google Scholar 

  49. Ferro-Luzzi A, James WPT, Kafatos A (2002) The high-fat Greek diet: a recipe for all? Eur J Clin Nutr 56:796–809

    Article  CAS  PubMed  Google Scholar 

  50. Bes-Rastrollo M, Sanchez-Villegas A, De La Fuente C, De Irala J, Martinez JA, Martinez-Gonzalez MA (2006) 41:249–256

  51. Covas MI (2007) Olive oil and the cardiovascular system. Pharmacol Res 55:175–186

    Article  CAS  PubMed  Google Scholar 

  52. Martinez-González MA, Sánchez-Villegas A, De Irala J, Marti A, Martínez JA (2002) Mediterranean diet and stroke: objectives and design of the SUN Project. Nutr Neurosci 5:65–73

    Article  Google Scholar 

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Acknowledgments

We thank A. Pino Blanes for its excellent technical assistance and K. Shashok for translating parts of the manuscript into English.

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Correspondence to J. P. De La Cruz.

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This study was partially supported by a grant from the Ministerio de Ciencia y Tecnología, Spain (AGL−04-7935-C03-02).

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González-Correa, J.A., Muñoz-Marín, J., Arrebola, M.M. et al. Dietary Virgin Olive Oil Reduces Oxidative Stress and Cellular Damage in Rat Brain Slices Subjected to Hypoxia–Reoxygenation. Lipids 42, 921–929 (2007). https://doi.org/10.1007/s11745-007-3097-6

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  • DOI: https://doi.org/10.1007/s11745-007-3097-6

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