Opposing actions of rosiglitazone and resveratrol on mineralization in human vascular smooth muscle cells

Journal of Molecular and Cellular Cardiology

Volumn 51, Issue 5, 2011, Pages 862-871

  Bruedigam, Claudia ^a   Eijken, Marco ^a   Koedam, Marijke ^a   Chiba, Hideki ^b   Van Leeuwen, Johannes P T M ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Mineralization; Osteoblast like differentiation; Oxidative stress; Resveratrol; Rosiglitazone; Vascular smooth muscle cell

Indexed keywords

CASPASE; MESSENGER RNA; REACTIVE OXYGEN METABOLITE; RESVERATROL; ROSIGLITAZONE;

APOPTOSIS; ARTICLE; CALORIC RESTRICTION; CELL DIFFERENTIATION; CELL STIMULATION; CONTROLLED STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG ANTAGONISM; DRUG MECHANISM; ENZYME INDUCTION; GENE EXPRESSION; HUMAN; HUMAN CELL; IN VITRO STUDY; MINERALIZATION; OSTEOBLAST; OXIDATIVE STRESS; PRIORITY JOURNAL; SMOOTH MUSCLE FIBER; VASCULAR SMOOTH MUSCLE;

APOPTOSIS; ATHEROSCLEROSIS; CASPASES; CELL DIFFERENTIATION; CELLS, CULTURED; DIABETES MELLITUS; HUMANS; HYPOGLYCEMIC AGENTS; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; OXIDATIVE STRESS; SIGNAL TRANSDUCTION; STILBENES; THIAZOLIDINEDIONES; UP-REGULATION;

EID: 80053286381     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2011.07.020     Document Type: Article

References (91)

1. Maayan C., Peleg O., Eyal F., Mogle P., Rosenmann E., Bar Ziv J. Idiopathic infantile arterial calcification: a case report and review of the literature. Eur J Pediatr 1984, 142(3):211-215.
2. Singleton E.B., Merten D.F. An unusual syndrome of widened medullary cavities of the metacarpals and phalanges, aortic calcification and abnormal dentition. Pediatr Radiol Mar 1973, 1(1):2-7.
3. Pope F.M. Autosomal dominant Pseudoxanthoma elasticum. J Med Genet Jun 1974, 11(2):152-157.
4. Breslow J.L. Mouse models of atherosclerosis. Science May 3 1996, 272(5262):685-688.
5. Detrano R.C., Wong N.D., Doherty T.M., Shavelle R. Prognostic significance of coronary calcific deposits in asymptomatic high-risk subjects. Am J Med Apr 1997, 102(4):344-349.
6. Wexler L., Brundage B., Crouse J., Detrano R., Fuster V., Maddahi J., et al. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group. Circulation Sep 1 1996, 94(5):1175-1192.
7. Zhang L., Zalewski A., Liu Y., Mazurek T., Cowan S., Martin J.L., et al. Diabetes-induced oxidative stress and low-grade inflammation in porcine coronary arteries. Circulation Jul 29 2003, 108(4):472-478.
8. Tintut Y., Patel J., Territo M., Saini T., Parhami F., Demer L.L. Monocyte/macrophage regulation of vascular calcification in vitro. Circulation Feb 5 2002, 105(5):650-655.
9. Sorescu G.P., Song H., Tressel S.L., Hwang J., Dikalov S., Smith D.A., et al. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1-based NADPH oxidase. Circ Res Oct 15 2004, 95(8):773-779.
10. Mody N., Parhami F., Sarafian T.A., Demer L.L. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med Aug 15 2001, 31(4):509-519.
11. Sutra T., Morena M., Bargnoux A.S., Caporiccio B., Canaud B., Cristol J.P. Superoxide production: a procalcifying cell signalling event in osteoblastic differentiation of vascular smooth muscle cells exposed to calcification media. Free Radic Res Sep 2008, 42(9):789-797.
12. Byon C.H., Javed A., Dai Q., Kappes J.C., Clemens T.L., Darley-Usmar V.M., et al. Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J Biol Chem May 30 2008, 283(22):15319-15327.
13. You H., Yang H., Zhu Q., Li M., Xue J., Gu Y., et al. Advanced oxidation protein products induce vascular calcification by promoting osteoblastic trans-differentiation of smooth muscle cells via oxidative stress and ERK pathway. Ren Fail 2009, 31(4):313-319.
14. Liu H., Yuan L., Xu S., Wang K. Endothelial cell and macrophage regulation of vascular smooth muscle cell calcification modulated by cholestane-3beta, 5alpha, 6beta-triol. Cell Biol Int Sep 2007, 31(9):900-907.
15. Dwyer J.R., Sever N., Carlson M., Nelson S.F., Beachy P.A., Parhami F. Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells. J Biol Chem Mar 23 2007, 282(12):8959-8968.
16. Lynch M.P., Capparelli C., Stein J.L., Stein G.S., Lian J.B. Apoptosis during bone-like tissue development in vitro. J Cell Biochem Jan 1 1998, 68(1):31-49.
17. Proudfoot D., Skepper J.N., Hegyi L., Bennett M.R., Shanahan C.M., Weissberg P.L. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res Nov 24 2000, 87(11):1055-1062.
18. Liberman M., Bassi E., Martinatti M.K., Lario F.C., Wosniak J., Pomerantzeff P.M., et al. Oxidant generation predominates around calcifying foci and enhances progression of aortic valve calcification. Arterioscler Thromb Vasc Biol Mar 2008, 28(3):463-470.
19. Clarke M.C., Littlewood T.D., Figg N., Maguire J.J., Davenport A.P., Goddard M., et al. Chronic apoptosis of vascular smooth muscle cells accelerates atherosclerosis and promotes calcification and medial degeneration. Circ Res Jun 20 2008, 102(12):1529-1538.
20. Clarke M.C., Figg N., Maguire J.J., Davenport A.P., Goddard M., Littlewood T.D., et al. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat Med Sep 2006, 12(9):1075-1080.
21. Duan X., Zhou Y., Teng X., Tang C., Qi Y. Endoplasmic reticulum stress-mediated apoptosis is activated in vascular calcification. Biochem Biophys Res Commun Oct 2 2009, 387(4):694-699.
22. Nissen S.E., Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med Jun 14 2007, 356(24):2457-2471.
23. Singh S., Loke Y.K., Furberg C.D. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA Sep 12 2007, 298(10):1189-1195.
24. Home P.D., Pocock S.J., Beck-Nielsen H., Curtis P.S., Gomis R., Hanefeld M., et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet Jun 20 2009, 373(9681):2125-2135.
25. Home P.D., Pocock S.J., Beck-Nielsen H., Gomis R., Hanefeld M., Jones N.P., et al. Rosiglitazone evaluated for cardiovascular outcomes - an interim analysis. N Engl J Med Jul 5 2007, 357(1):28-38.
26. Lago R.M., Singh P.P., Nesto R.W. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet Sep 29 2007, 370(9593):1129-1136.
27. Bruemmer D., Yin F., Liu J., Berger J.P., Sakai T., Blaschke F., et al. Regulation of the growth arrest and DNA damage-inducible gene 45 (GADD45) by peroxisome proliferator-activated receptor gamma in vascular smooth muscle cells. Circ Res Aug 22 2003, 93(4):e38-e47.
28. Lin Y., Zhu X., McLntee F.L., Xiao H., Zhang J., Fu M., et al. Interferon regulatory factor-1 mediates PPARgamma-induced apoptosis in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol Feb 2004, 24(2):257-263.
29. Okura T., Nakamura M., Takata Y., Watanabe S., Kitami Y., Hiwada K. Troglitazone induces apoptosis via the p53 and Gadd45 pathway in vascular smooth muscle cells. Eur J Pharmacol Nov 3 2000, 407(3):227-235.
30. Redondo S., Ruiz E., Santos-Gallego C.G., Padilla E., Tejerina T. Pioglitazone induces vascular smooth muscle cell apoptosis through a peroxisome proliferator-activated receptor-gamma, transforming growth factor-beta1, and a Smad2-dependent mechanism. Diabetes Mar 2005, 54(3):811-817.
31. Ruiz E., Redondo S., Gordillo-Moscoso A., Tejerina T. Pioglitazone induces apoptosis in human vascular smooth muscle cells from diabetic patients involving the transforming growth factor-beta/activin receptor-like kinase-4/5/7/Smad2 signaling pathway. J Pharmacol Exp Ther May 2007, 321(2):431-438.
32. Eijken M., Swagemakers S., Koedam M., Steenbergen C., Derkx P., Uitterlinden A.G., et al. The activin A-follistatin system: potent regulator of human extracellular matrix mineralization. FASEB J Sep 2007, 21(11):2949-2960.
33. Mori K., Shioi A., Jono S., Nishizawa Y., Morii H. Dexamethasone enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol Sep 1999, 19(9):2112-2118.
34. Bruedigam C., Koedam M., Chiba H., Eijken M., van Leeuwen J.P. Evidence for multiple peroxisome proliferator-activated receptor gamma transcripts in bone: fine-tuning by hormonal regulation and mRNA stability. FEBS Lett May 14 2008, 582(11):1618-1624.
35. Shioi A., Nishizawa Y., Jono S., Koyama H., Hosoi M., Morii H. Beta-glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb Vasc Biol Nov 1995, 15(11):2003-2009.
36. Garfinkel A., Tintut Y., Petrasek D., Bostrom K., Demer L.L. Pattern formation by vascular mesenchymal cells. Proc Natl Acad Sci U S A Jun 22 2004, 101(25):9247-9250.
37. Griendling K.K., Sorescu D., Lassegue B., Ushio-Fukai M. Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol Oct 2000, 20(10):2175-2183.
38. Ellmark S.H., Dusting G.J., Fui M.N., Guzzo-Pernell N., Drummond G.R. The contribution of Nox4 to NADPH oxidase activity in mouse vascular smooth muscle. Cardiovasc Res Feb 1 2005, 65(2):495-504.
39. Itoh S., Umemoto S., Hiromoto M., Toma Y., Tomochika Y., Aoyagi S., et al. Importance of NAD(P)H oxidase-mediated oxidative stress and contractile type smooth muscle myosin heavy chain SM2 at the early stage of atherosclerosis. Circulation May 14 2002, 105(19):2288-2295.
40. Kawada N., Seki S., Inoue M., Kuroki T. Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells. Hepatology May 1998, 27(5):1265-1274.
41. Marques F.Z., Markus M.A., Morris B.J. Resveratrol: cellular actions of a potent natural chemical that confers a diversity of health benefits. Int J Biochem Cell Biol Nov 2009, 41(11):2125-2128.
42. Penumathsa S.V., Maulik N. Resveratrol: a promising agent in promoting cardioprotection against coronary heart disease. Can J Physiol Pharmacol Apr 2009, 87(4):275-286.
43. Soleas G.J., Diamandis E.P., Goldberg D.M. Resveratrol: a molecule whose time has come? And gone?. Clin Biochem Mar 1997, 30(2):91-113.
44. Bhat K.P.L., Kosmeder J.W., Pezzuto J.M. Biological effects of resveratrol. Antioxid Redox Signal Dec 2001, 3(6):1041-1064.
45. Dalfino G., Simone S., Porreca S., Cosola C., Balestra C., Manno C., et al. Bone morphogenetic protein-2 may represent the molecular link between oxidative stress and vascular stiffness in chronic kidney disease. Atherosclerosis Aug 2010, 211(2):418-423.
46. San Martin A., Du P., Dikalova A., Lassegue B., Aleman M., Gongora M.C., et al. Reactive oxygen species-selective regulation of aortic inflammatory gene expression in type 2 diabetes. Am J Physiol Heart Circ Physiol May 2007, 292(5):H2073-H2082.
47. Ridker P.M., Cook N.R., Cheng S., Erlich H.A., Lindpaintner K., Plutzky J., et al. Alanine for proline substitution in the peroxisome proliferator-activated receptor gamma-2 (PPARG2) gene and the risk of incident myocardial infarction. Arterioscler Thromb Vasc Biol May 1 2003, 23(5):859-863.
48. Wang X.L., Oosterhof J., Duarte N. Peroxisome proliferator-activated receptor gamma C161->T polymorphism and coronary artery disease. Cardiovasc Res Dec 1999, 44(3):588-594.
49. Chen Z., Ishibashi S., Perrey S., Osuga J., Gotoda T., Kitamine T., et al. Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL. Arterioscler Thromb Vasc Biol Mar 2001, 21(3):372-377.
50. Levi Z., Shaish A., Yacov N., Levkovitz H., Trestman S., Gerber Y., et al. Rosiglitazone (PPARgamma-agonist) attenuates atherogenesis with no effect on hyperglycaemia in a combined diabetes-atherosclerosis mouse model. Diabetes Obes Metab Jan 2003, 5(1):45-50.
51. Calkin A.C., Forbes J.M., Smith C.M., Lassila M., Cooper M.E., Jandeleit-Dahm K.A., et al. Rosiglitazone attenuates atherosclerosis in a model of insulin insufficiency independent of its metabolic effects. Arterioscler Thromb Vasc Biol Sep 2005, 25(9):1903-1909.
52. Li A.C., Brown K.K., Silvestre M.J., Willson T.M., Palinski W., Glass C.K. Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin Invest Aug 2000, 106(4):523-531.
53. Lim S., Jin C.J., Kim M., Chung S.S., Park H.S., Lee I.K., et al. PPARgamma gene transfer sustains apoptosis, inhibits vascular smooth muscle cell proliferation, and reduces neointima formation after balloon injury in rats. Arterioscler Thromb Vasc Biol Apr 2006, 26(4):808-813.
54. Koshiyama H., Shimono D., Kuwamura N., Minamikawa J., Nakamura Y. Rapid communication: inhibitory effect of pioglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab Jul 2001, 86(7):3452-3456.
55. Minamikawa J., Tanaka S., Yamauchi M., Inoue D., Koshiyama H. Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab May 1998, 83(5):1818-1820.
56. Johnson R.C., Leopold J.A., Loscalzo J. Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res Nov 10 2006, 99(10):1044-1059.
57. Doherty T.M., Asotra K., Fitzpatrick L.A., Qiao J.H., Wilkin D.J., Detrano R.C., et al. Calcification in atherosclerosis: bone biology and chronic inflammation at the arterial crossroads. Proc Natl Acad Sci U S A Sep 30 2003, 100(20):11201-11206.
58. Budoff M.J. Atherosclerosis imaging and calcified plaque: coronary artery disease risk assessment. Prog Cardiovasc Dis 2003, 46(2):135-148.
59. Speer M.Y., Giachelli C.M. Regulation of cardiovascular calcification. Cardiovasc Pathol 2004, 13(2):63-70.
60. Schinke T., Karsenty G. Vascular calcification - a passive process in need of inhibitors. Nephrol Dial Transplant 2000, 15(9):1272-1274.
61. Narayanan P.K., Hart T., Elcock F., Zhang C., Hahn L., McFarland D., et al. Troglitazone-induced intracellular oxidative stress in rat hepatoma cells: a flow cytometric assessment. Cytometry A 2003, 52(1):28-35.
62. Lennon A.M., Ramauge M., Dessouroux A., Pierre M. MAP kinase cascades are activated in astrocytes and preadipocytes by 15-deoxy-delta(12-14)-prostaglandin J(2) and the thiazolidinedione ciglitazone through peroxisome proliferator activator receptor gamma-independent mechanisms involving reactive oxygenated species. J Biol Chem 2002, 277(33):29681-29685.
63. Huang W.C., Chio C.C., Chi K.H., Wu H.M., Lin W.W. Superoxide anion-dependent Raf/MEK/ERK activation by peroxisome proliferator activated receptor gamma agonists 15-deoxy-delta(12,14)-prostaglandin J(2), ciglitazone, and GW1929. Exp Cell Res 2002, 277(2):192-200.
64. Bruedigam C., Eijken M., Koedam M., van de Peppel J., Drabek K., Chiba H., et al. A new concept underlying stem cell lineage skewing that explains the detrimental effects of thiazolidinediones on bone. Stem Cells 2010, 28(5):915-927.
65. Potenza M.A., Gagliardi S., De Benedictis L., Zigrino A., Tiravanti E., Colantuono G., et al. Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature. Am J Physiol Endocrinol Metab 2009, 297(3):E685-E694.
66. Hwang J., Kleinhenz D.J., Rupnow H.L., Campbell A.G., Thule P.M., Sutliff R.L., et al. The PPARgamma ligand, rosiglitazone, reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice. Vascul Pharmacol 2007, 46(6):456-462.
67. Xiang L., Dearman J., Abram S.R., Carter C., Hester R.L. Insulin resistance and impaired functional vasodilation in obese Zucker rats. Am J Physiol Heart Circ Physiol 2008, 294(4):H1658-H1666.
68. Gao L., Mann G.E. Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling. Cardiovasc Res 2009, 82(1):9-20.
69. Majithiya J.B., Balaraman R. Time-dependent changes in antioxidant enzymes and vascular reactivity of aorta in streptozotocin-induced diabetic rats treated with curcumin. J Cardiovasc Pharmacol 2005, 46(5):697-705.
70. Opara E.C., Abdel-Rahman E., Soliman S., Kamel W.A., Souka S., Lowe J.E., et al. Depletion of total antioxidant capacity in type 2 diabetes. Metabolism 1999, 48(11):1414-1417.
71. Feinstein D.L., Spagnolo A., Akar C., Weinberg G., Murphy P., Gavrilyuk V., et al. Receptor-independent actions of PPAR thiazolidinedione agonists: is mitochondrial function the key?. Biochem Pharmacol 15 2005, 70(2):177-188.
72. Soroceanu M.A., Miao D., Bai X.Y., Su H., Goltzman D., Karaplis A.C. Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis. J Endocrinol 2004, 183(1):203-216.
73. Bonewald L.F. The amazing osteocyte. J Bone Miner Res 2011, 26(2):229-238.
74. Grey A., Bolland M., Gamble G., Wattie D., Horne A., Davidson J., et al. The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 2007, 92(4):1305-1310.
75. Tseng W., Graham L.S., Geng Y., Reddy A., Lu J., Effros R.B., et al. PKA-induced receptor activator of NF-kappaB ligand (RANKL) expression in vascular cells mediates osteoclastogenesis but not matrix calcification. J Biol Chem 2010, 285(39):29925-29931.
76. Jeziorska M., McCollum C., Wooley D.E. Observations on bone formation and remodelling in advanced atherosclerotic lesions of human carotid arteries. Virchows Arch 1998, 433(6):559-565.
77. Jeziorska M., McCollum C., Woolley D.E. Calcification in atherosclerotic plaque of human carotid arteries: associations with mast cells and macrophages. J Pathol 1998, 185(1):10-17.
78. Zhou H., Shang L., Li X., Zhang X., Gao G., Guo C., et al. Resveratrol augments the canonical Wnt signaling pathway in promoting osteoblastic differentiation of multipotent mesenchymal cells. Exp Cell Res 2009, 315(17):2953-2962.
79. Kao C.L., Tai L.K., Chiou S.H., Chen Y.J., Lee K.H., Chou S.J., et al. Resveratrol promotes osteogenic differentiation and protects against dexamethasone damage in murine induced pluripotent stem cells. Stem Cells Dev Feb 2010, 19(2):247-258.
80. Dai Z., Li Y., Quarles L.D., Song T., Pan W., Zhou H., et al. Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine 2007, 14(12):806-814.
81. Mizutani K., Ikeda K., Kawai Y., Yamori Y. Resveratrol stimulates the proliferation and differentiation of osteoblastic MC3T3-E1 cells. Biochem Biophys Res Commun 1998, 253(3):859-863.
82. Kobayashi H., Gao Y., Ueta C., Yamaguchi A., Komori T. Multilineage differentiation of Cbfa1-deficient calvarial cells in vitro. Biochem Biophys Res Commun 2000, 273(2):630-636.
83. Liu W., Toyosawa S., Furuichi T., Kanatani N., Yoshida C., Liu Y., et al. Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J Cell Biol 2001, 155(1):157-166.
84. Eijken M., Meijer I.M., Westbroek I., Koedam M., Chiba H., Uitterlinden A.G., et al. Wnt signaling acts and is regulated in a human osteoblast differentiation dependent manner. J Cell Biochem 2008, 104(2):568-579.
85. Li X., Liu P., Liu W., Maye P., Zhang J., Zhang Y., et al. Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat Genet 2005, 37(9):945-952.
86. Siddhivarn C., Banes A., Champagne C., Riche E.L., Weerapradist W., Offenbacher S. Mechanical loading and delta12prostaglandin J2 induce bone morphogenetic protein-2, peroxisome proliferator-activated receptor gamma-1, and bone nodule formation in an osteoblastic cell line. J Periodontal Res 2007, 42(5):383-392.
87. Zhou X., Sheng Y., Yang R., Kong X. Nicotine promotes cardiomyocyte apoptosis via oxidative stress and altered apoptosis-related gene expression. Cardiology 2010, 115(4):243-250.
88. Fukao H., Ijiri Y., Miura M., Hashimoto M., Yamashita T., Fukunaga C., et al. Effect of trans-resveratrol on the thrombogenicity and atherogenicity in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Blood Coagul Fibrinolysis 2004, 15(6):441-446.
89. Rocha K.K., Souza G.A., Ebaid G.X., Seiva F.R., Cataneo A.C., Novelli E.L. Resveratrol toxicity: effects on risk factors for atherosclerosis and hepatic oxidative stress in standard and high-fat diets. Food Chem Toxicol 2009, 47(6):1362-1367.
90. Goldberg D.M., Yan J., Soleas G.J. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem 2003, 36(1):79-87.
91. Walle T., Hsieh F., DeLegge M.H., Oatis J.E., Walle U.K. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 2004, 32(12):1377-1382.