Bioavailability studies in animals and humans fed with extravirgin olive oil demonstrated that hydroxytyrosol and tyrosol, the major simple phenolic compounds in extravirgin olive oil, are dose-dependently absorbed and excreted. Once absorbed, they undergo extensive metabolism; hydroxytyrosol and tyrosol concentrate mainly in the kidney, where they may exert an important role in the prevention of oxidative stress induced renal dysfunction. In this study we monitored the ability of hydroxytyrosol and tyrosol to protect renal cells (LLC-PK1) following oxidative damage induced by H2O2. Oxidative stress was evaluated by monitoring the changes of the membrane lipid fraction. Hydroxytyrosol exerted a significant antioxidant action, inhibiting the production of MDA, fatty acids hydroperoxides and 7-ketocholesterol, major oxidation products of unsaturated fatty acids and cholesterol, and thus protecting the cells from H2O2-induced damage. Tyrosol, instead, in this experimental model, did not exert any protective effect.
Andreoli SP McAteer JA (1990) Reactive oxygen molecule-mediated injury in endothelial and renal tubular epithelial cells in vitro. Kidney Int38: 785–794.
2.
Baliga R Ueda N Walker PD Shah SV (1999) Oxidant mechanisms in toxic acute renal failure. Drug Metab Rev31: 971–997.
3.
Banni S Day BW Ewans RW Corongiu FP Lombardi B (1994) Liquid chromatografy-mass spectometric analysis of conjugated diene fatty acid in milk, dairy products and lamb tissues. J Nutr Biochem7: 150–155.
4.
Barrouillet MP Moiret A Cambar J (1999) Protective effects of polyphenols against cadmium-induced glomerular mesangial cell myocontracture. Arch Toxicol73: 485–488.
5.
Bertelli AA Migliori M Panichi V Longoni B Origlia N Ferretti A (2002) Oxidative stress and inflammatory reaction modulation by white wine. Ann N Y Acad Sci957: 295–301.
6.
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem72: 248–254.
7.
Bu Y Rho S Kim J Kim KY Lee DH Kim SY (2007) Neuroprotective effect of tyrosol on transient focal cerebral ischemia in rats. Neurosci Lett414: 218–221.
8.
Cantiello HF Scott JA Rabito CA (1987) Conductive Na+ transport in an epithelial cell line (LLC-PK1) with characteristics of proximal tubular cells. Am J Physiol252: F590–F597.
9.
Carluccio MA Siculella L Ancora MA Massaro M Scoditti E Storelli C (2003) Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler Thromb Vasc Biol23: 622–629.
10.
Caruso D Berra B Giavarini F Cortesi N Fedeli E Galli G (1999) Effect of virgin olive oil phenolic compounds on in vitro oxidation of human low density lipoproteins. Nutr Metab Cardiovasc Dis9: 102–107.
11.
Caruso D Visioli F Patelli R Galli C Galli G (2001) Urinary excretion of olive oil phenols and their metabolites in humans. Metabolism50: 1426–1428.
12.
de la Puerta R Martinez Dominguez ME Ruiz-Gutierrez V Flavill JA Hoult JR (2001) Effects of virgin olive oil phenolics on scavenging of reactive nitrogen species and upon nitrergic neurotransmission. Life Sci69: 1213–1222.
13.
de la Puerta R Ruiz Gutierrez V Hoult JR (1999) Inhibition of leukocyte 5-lipoxygenase by phenolics from virgin olive oil. Biochem Pharmacol57: 445–449.
14.
de la Torre-Carbot K Jauregui O Gimeno E Castellote AI Lamuela-Raventos RM Lopez-Sabater MC (2005) Characterization and quantification of phenolic compounds in olive oils by solid-phase extraction, HPLC-DAD, and HPLC-MS/MS. J Agric Food Chem53: 4331–4340.
15.
Deiana M Aruoma OI Bianchi ML Spencer JP Kaur H Halliwell B (1999) Inhibition of peroxynitrite dependent DNA base modification and tyrosine nitration by the extra virgin olive oil-derived antioxidant hydroxytyrosol. Free Radic Biol Med26: 762–769.
16.
Deiana M Rosa A Corona G Atzeri A Incani A Visioli F (2007) Protective effect of olive oil minor polar components against oxidative damage in rats treated with ferric-nitrilotriacetate. Food Chem Toxicol45: 2434–2440.
17.
Di Benedetto R Vari R Scazzocchio B Filesi C Santangelo C Giovannini C (2007) Tyrosol, the major extra virgin olive oil compound, restored intracellular antioxidant defences in spite of its weak antioxidative effectiveness. Nutr Metab Cardiovasc Dis17: 535–545.
18.
Fidanza F Puddu V Imbimbo AB Menotti A Keys A (1970) Coronary heart disease in seven countries. VII. Five-year experience in rural Italy. Circulation41: I63–I75.
19.
Fiorillo C Oliviero C Rizzuti G Nediani C Pacini A Nassi P (1998) Oxidative stress and antioxidant defenses in renal patients receiving regular haemodialysis. Clin Chem Lab Med36: 149–153.
20.
Folch J Lees M Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem226: 497–509.
21.
Fryer MJ (1997) Vitamin E may slow kidney failure owing to oxidative stress. Redox Rep3: 259–261.
22.
Giovannini C Straface E Modesti D Coni E Cantafora A De Vincenzi M (1999) Tyrosol, the major olive oil biophenol, protects against oxidized-LDL-induced injury in Caco-2 cells. J Nutr129: 1269–1277.
23.
Giovannini L Migliori M Filippi C Origlia N Panichi V Falchi M (2002) Inhibitory activity of the white wine compounds, tyrosol and caffeic acid, on lipopolysaccharide-induced tumor necrosis factor-alpha release in human peripheral blood mononuclear cells. Int J Tissue React24: 53–56.
24.
Gordon MH Paiva-Martins F Almeida M (2001) Antioxidant activity of hydroxytyrosol acetate compared with that of other olive oil polyphenols. J Agric Food Chem49: 2480–2485.
25.
Greiber S Kramer-Guth A Pavenstadt H Gutenkunst M Schollmeyer P Wanner C (1996) Effects of lipoprotein(a) on mesangial cell proliferation and viability. Nephrol Dial Transplant11: 778–785.
26.
Gutierrez VR de la Puerta R Catala A (2001) The effect of tyrosol, hydroxytyrosol and oleuropein on the non-enzymatic lipid peroxidation of rat liver microsomes. Mol Cell Biochem217: 35–41.
27.
Hahn S Krieg RJ Hisano S Chan W Kuemmerle NB Saborio P (1999) Vitamin E suppresses oxidative stress and glomerulosclerosis in rat remnant kidney. Pediatr Nephrol13: 195–198.
28.
Ichikawa I Kiyama S Yoshioka T (1994) Renal antioxidant enzymes: their regulation and function. Kidney Int45: 1–9.
29.
Kinter M Wolstenholme JT Thornhill BA Newton EA McCormick ML Chevalier RL (1999) Unilateral ureteral obstruction impairs renal antioxidant enzyme activation during sodium depletion. Kidney Int55: 1327–1334.
30.
Kitamura M Ishikawa Y (1999) Oxidant-induced apoptosis of glomerular cells: intracellular signaling and its intervention by bioflavinoid. Kidney Int56: 1223–1229.
31.
Klahr S (1997) Oxygen radicals and renal diseases. Miner Electrolyte Metab23: 140–143.
32.
Klahr S (2001) Urinary tract obstruction. Semin Nephrol21: 133–145.
33.
Kubo K Saito M Tadokoro T Maekawa A (1997) Changes in susceptibility of tissues to lipid peroxidation after ingestion of various levels of docosahexaenoic acid and vitamin E. Br J Nutr78: 655–669.
34.
Manna C Galletti P Cucciolla V Moltedo O Leone A Zappia V (1997) The protective effect of the olive oil polyphenol (3,4-dihydroxyphenyl)-ethanol counteracts reactive oxygen metabolite-induced cytotoxicity in Caco-2 cells. J Nutr127: 286–292.
35.
Martin-Mateo MC Sanchez-Portugal M Iglesias S de Paula A Bustamante J (1999) Oxidative stress in chronic renal failure. Ren Fail21: 155–167.
36.
Martinez-Dominguez E de la Puerta R Ruiz-Gutierrez V (2001) Protective effects upon experimental inflammation models of a polyphenol-supplemented virgin olive oil diet. Inflamm Res50: 102–106.
37.
Meng X Reeves WB (2000) Effects of chloride channel inhibitors on H(2)O(2)-induced renal epithelial cell injury. Am J Physiol Renal Physiol278: F83–F90.
38.
Miro-Casas E Covas MI Fito M Farre-Albadalejo M Marrugat J de la Torre R (2003) Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans. Eur J Clin Nutr57: 186–190.
39.
Moreno-Manzano V Ishikawa Y Lucio-Cazana J Kitamura M (2000) Selective involvement of superoxide anion, but not downstream compounds hydrogen peroxide and peroxynitrite, in tumor necrosis factor-alpha-induced apoptosis of rat mesangial cells. J Biol Chem275: 12684–12691.
40.
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods65: 55–63.
41.
Ou ZL Natori Y Natori Y (1999) Gene expression of CC chemokines in experimental acute tubulointerstitial nephritis. J Lab Clin Med133: 41–47.
42.
Owen RW Giacosa A Hull WE Haubner R Wurtele G Spiegelhalder B (2000) Olive-oil consumption and health: the possible role of antioxidants. Lancet Oncol1: 107–112.
43.
Ozaki M Yamada Y Matoba K Otani H Mune M Yukawa S (1999) Phospholipase A2 activity in ox-LDL-stimulated mesangial cells and modulation by alpha-tocopherol. Kidney Int Suppl71: S171–S173.
44.
Paller MS Weber K Patten M (1998) Nitric oxide-mediated renal epithelial cell injury during hypoxia and reoxygenation. Ren Fail20: 459–469.
45.
Perantoni A Berman JJ (1979) Properties of Wilms' tumor line (TuWi) and pig kidney line (LLC-PK1) typical of normal kidney tubular epithelium. In Vitro15: 446–454.
46.
Petroni A Blasevich M Salami M Papini N Montedoro GF Galli C (1995) Inhibition of platelet aggregation and eicosanoid production by phenolic components of olive oil. Thromb Res78: 151–160.
47.
Rodrigo R Rivera G (2002) Renal damage mediated by oxidative stress: a hypothesis of protective effects of red wine. Free Radic Biol Med33: 409–422.
48.
Romero C Medina E Vargas J Brenes M De Castro A (2007) In vitro activity of olive oil polyphenols against Helicobacter pylori. J Agric Food Chem55: 680–686.
49.
Saija A Tomaino A Lo Cascio R Princi P Uccella N Bonina F (1998a) In vitro evaluation of the antioxidat activity and biomembrane interaction of the plant phenols oleuropein and hydroxytyrosol. Int J Pharm166: 123–133.
50.
Saija A Tomaino A Lo Cascio R Rapisarda P Dederen JC (1998b) In vitro antioxidant activity and in vivo photoprotective effect of a red orange extract. Int J Cosmet Sci20: 331–342.
51.
Sakatsume M Kadomura M Sakata I Imai N Kondo D Osawa Y (2001) Novel glomerular lipoprotein deposits associated with apolipoprotein E2 homozygosity. Kidney Int59: 1911–1918.
52.
Salahudeen AK (1995) Role of lipid peroxidation in H2O2-induced renal epithelial (LLC-PK1) cell injury. Am J Physiol268: F30–F38.
53.
Salami M Galli C De Angelis L Visioli F (1995) Formation of F2-isoprostanes in oxidized low density lipoprotein: inhibitory effect of hydroxytyrosol. Pharmacol Res31: 275–279.
54.
Scheuer H Gwinner W Hohbach J Grone EF Brandes RP Malle E (2000) Oxidant stress in hyperlipidemia-induced renal damage. Am J Physiol Renal Physiol278: F63–F74.
55.
Shah S (2001) Role of iron in progressive renal disease. Am J Kidney Dis37: S30–S33.
56.
Sheridan AM Fitzpatrick S Wang C Wheeler DC Lieberthal W (1996) Lipid peroxidation contributes to hydrogen peroxide induced cytotoxicity in renal epithelial cells. Kidney Int49: 88–93.
57.
Singh D Kaur R Chander V Chopra K (2006) Antioxidants in the prevention of renal disease. J Med Food9: 443–450.
58.
Templar J Kon SP Milligan TP Newman DJ Raftery MJ (1999) Increased plasma malondialdehyde levels in glomerular disease as determined by a fully validated HPLC method. Nephrol Dial Transplant14: 946–951.
59.
Vanholder R Sever MS Erek E Lameire N (2000) Rhabdomyolysis. J Am Soc Nephrol11: 1553–1561.
60.
Vauzour D Vafeiadou K Corona G Pollard SE Tzounis X Spencer JP (2007) Champagne wine polyphenols protect primary cortical neurons against peroxynitrite-induced injury. J Agric Food Chem55: 2854–2860.
61.
Visioli F Bellomo G Montedoro G Galli C (1995) Low density lipoprotein oxidation is inhibited in vitro by olive oil constituents. Atherosclerosis117: 25–32.
62.
Visioli F Galli C Bornet F Mattei A Patelli R Galli G (2000) Olive oil phenolics are dose-dependently absorbed in humans. FEBS Lett468: 159–160.
63.
Visioli F Poli A Gall C (2002) Antioxidant and other biological activities of phenols from olives and olive oil. Med Res Rev22: 65–75.
64.
Wanner C Greiber S Kramer-Guth A Heinloth A Galle J (1997) Lipids and progression of renal disease: role of modified low density lipoprotein and lipoprotein(a). Kidney Int Suppl63: S102–S106.
65.
Waterman E Lockwood B (2007) Active components and clinical applications of olive oil. Altern Med Rev12: 331–342.
66.
Zager RA Burkhart K (1997) Myoglobin toxicity in proximal human kidney cells: roles of Fe, Ca2+, H2O2, and terminal mitochondrial electron transport. Kidney Int51: 728–738.
