Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) in vitro and in vivo

European Journal of Pharmacology

Volumn 505, Issue 1-3, 2004, Pages 213-221

  Tavridou, Anna ^a,b   Manolopoulos, Vangelis G ^a  

^a DEMOCRITUS UNIVERSITY OF THRACE   (Greece)

^b Dept of Preclinical Pharmacology   (Greece)

Author keywords

(Rabbit); 2 Biphenylmorpholine compound; Antioxidant; Atherosclerosis; Copper mediated oxidation; Low density lipoprotein

Indexed keywords

2 (4 BIPHENYL) 2 (3 NITROOXYPROPOXY) 4 METHYLMORPHOLINE HYDROBROMIDE; 2 (4 BIPHENYL) 4 METHYL OCTAHYDRO 1,4 BENZOXAZIN 2 OL HYDROBROMIDE; ANTIOXIDANT; ARACHIDONATE 12 LIPOXYGENASE; ARACHIDONATE 15 LIPOXYGENASE; COPPER; COPPER ION; EP 2300; EP 2302; EP 2306; LOW DENSITY LIPOPROTEIN; PEROXY RADICAL; PROBUCOL; SIMVASTATIN; THIOBARBITURIC ACID REACTIVE SUBSTANCE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIOXIDANT ACTIVITY; ARTICLE; ATHEROSCLEROSIS; CHELATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; ENZYME ACTIVITY; ENZYME INHIBITION; HYPERLIPIDEMIA; IC 50; INTERMETHOD COMPARISON; NONHUMAN; OXIDATION; PRIORITY JOURNAL; RABBIT; STATISTICAL SIGNIFICANCE;

ANIMALS; ANTIOXIDANTS; BIPHENYL COMPOUNDS; COPPER; DOSE-RESPONSE RELATIONSHIP, DRUG; FREE RADICAL SCAVENGERS; HUMANS; HYPERLIPIDEMIAS; LIPOPROTEINS, LDL; LIPOXYGENASE; MALE; MORPHOLINES; OXIDATION-REDUCTION; RABBITS; THIOBARBITURIC ACID REACTIVE SUBSTANCES; TIME FACTORS;

EID: 8844253955     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2004.10.047     Document Type: Article

References (41)

1. P.M. Abuja, K. Lohner, and R. Prassl Modification of the lipid-protein interaction in human low-density lipoprotein destabilizes ApoB-100 and decreases oxidizability Biochemistry 38 1999 3401 3408
2. M. Aviram, M. Rosenblat, C.L. Bisgaier, and R.S. Newton Atorvastatin and gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation Atherosclerosis 138 1998 271 280
3. J. Belkner, H. Stender, and H. Kuhn The rabbit 15-lipoxygenase preferentially oxygenates LDL cholesterol esters, and this reaction does not require vitamin E J. Biol. Chem. 273 1998 23225 23232
4. D.A. Bird, R.K. Tangirala, J. Fruebis, D. Steinberg, J.L. Witztum, and W. Palinski Effect of probucol on LDL oxidation and atherosclerosis in LDL receptor-deficient mice J. Lipid Res. 39 1998 1079 1090
5. I. Bjorkhem, A. Henriksson-Freyschuss, O. Breuer, U. Diczfalusy, L. Berglund, and P. Henriksson The antioxidant butylated hydroxytoluene protects against atherosclerosis Arterioscler. Thromb. 11 1991 15 22
6. M.S. Blois Antioxidant determination by the use of a stable free radical Nature 189 1958 1199 1200
7. M.J. Burkitt A critical overview of the chemistry of copper-dependent low density lipoprotein oxidation: roles of lipid hydroperoxides, alpha-tocopherol, thiols, and ceruloplasmin Arch. Biochem. Biophys. 394 2001 117 135
8. M.K. Cathcart, and V.A. Folcik Lipoxygenases and atherosclerosis: protection versus pathogenesis Free Radic. Biol. Med. 28 2000 1726 1734
9. M.Y. Chang, M. Sasahara, A. Chait, E.W. Raines, and R. Ross Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol: II. Cellular composition and proliferation Arterioscler. Thromb. Vasc. Biol. 15 1995 1631 1640
10. M.C. Chrysselis, E.A. Rekka, and P.N. Kourounakis Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity J. Med. Chem. 43 2000 609 612
11. M.C. Chrysselis, E.A. Rekka, I.C. Siskou, and P.N. Kourounakis Nitric oxide releasing morpholine derivatives as hypolipidemic and antioxidant agents J. Med. Chem. 45 2002 5406 5409
12. H. Esterbauer, G. Striegl, H. Puhl, and M. Rotheneder Continuous monitoring of in vitro oxidation of human low density lipoprotein Free Radic. Res. Commun. 6 1989 67 75
13. H. Esterbauer, J. Gebicki, H. Puhl, and G. Jurgens The role of lipid peroxidation and antioxidants in oxidative modification of LDL Free Radic. Biol. Med. 13 1992 341 390
14. H. Esterbauer, G. Wag, and H. Puhl Lipid peroxidation and its role in atherosclerosis Br. Med. Bull. 49 1993 566 576
15. A.M. Fogelman, I. Shechter, J. Seager, M. Hokom, J.S. Child, and P.A. Edwards Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages Proc. Natl. Acad. Sci. U. S. A. 77 1980 2214 2218
16. B. Garner, D. van Reyk, R.T. Dean, and W. Jessup Direct copper reduction by macrophages. Its role in low density lipoprotein oxidation J. Biol. Chem. 272 1997 6927 6935
17. T. Hiltunen, J. Luoma, T. Nikkari, and S. Yla-Herttuala Induction of 15-lipoxygenase mRNA and protein in early atherosclerotic lesions Circulation 92 1995 3297 3303
18. O. Hussein, S. Schlezinger, M. Rosenblat, S. Keidar, and M. Aviram Reduced susceptibility of low density lipoprotein (LDL) to lipid peroxidation after fluvastatin therapy is associated with the hypocholesterolemic effect of the drug and its binding to the LDL Atherosclerosis 128 1997 11 18
19. J. Johansson, A.G. Olsson, L. Bergstrand, L.S. Elinder, S. Nilsson, U. Erikson, J. Molgaard, I. Holme, and G. Walldius Lowering of HDL2b by probucol partly explains the failure of the drug to affect femoral atherosclerosis in subjects with hypercholesterolemia. A probucol quantitative regression Swedish trial (PQRST) report Arterioscler. Thromb. Vasc. Biol. 15 1995 1049 1056
20. H.A. Kleinveld, H.L. Hak-Lemmers, A.F. Stalenhoef, and P.N. Demacker Improved measurement of low-density-lipoprotein susceptibility to copper-induced oxidation: application of a short procedure for isolating low-density lipoprotein Clin. Chem. 38 1992 2066 2072
21. H.A. Kleinveld, P.N. Demacker, A.F. De Haan, and A.F. Stalenhoef Decreased in vitro oxidizability of low-density lipoprotein in hypercholesterolaemic patients treated with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors Eur. J. Clin. Investig. 23 1993 289 295
22. H. Kuhn, D. Heydeck, I. Hugou, and C. Gniwotta In vivo action of 15-lipoxygenase in early stages of human atherogenesis J. Clin. Invest. 99 1997 888 893
23. H.A. Lehr, B. Frei, A.M. Olofsson, T.E. Carew, and K.E. Arfors Protection from oxidized LDL-induced leukocyte adhesion to microvascular and macrovascular endothelium in vivo by vitamin C but not by vitamin E Circulation 91 1995 1525 1532
24. A.K. McNally, G.M. Chisolm III, D.W. Morel, and M.K. Cathcart Activated human monocytes oxidize low-density lipoprotein by a lipoxygenase-dependent pathway J. Immunol. 145 1990 254 259
25. N.E. Miller Associations of high-density lipoprotein subclasses and apolipoproteins with ischemic heart disease and coronary atherosclerosis Am. Heart J. 113 1987 589 597
26. C.K. Mukhopadhyay, B. Mazumder, P.F. Lindley, and P.L. Fox Identification of the prooxidant site of human ceruloplasmin: a model for oxidative damage by copper bound to protein surfaces Proc. Natl. Acad. Sci. U. S. A. 94 1997 11546 11551
27. L. Niculescu, C. Stancu, A. Sima, D. Toporan, and M. Simionescu The total peroxyl radical trapping potential in serum-an assay to define the stage of atherosclerosis J. Cell. Mol. Med. 5 2001 285 294
28. V.J. O'Leary, L. Tilling, G. Fleetwood, D. Stone, and V. Darley-Usmar The resistance of low density lipoprotein to oxidation promoted by copper and its use as an index of antioxidant therapy Atherosclerosis 119 1996 169 179
29. W. Palinski, M.E. Rosenfeld, S. Yla-Herttuala, G.C. Gurtner, S.S. Socher, S.W. Butler, S. Parthasarathy, T.E. Carew, D. Steinberg, and J.L. Witztum Low density lipoprotein undergoes oxidative modification in vivo Proc. Natl. Acad. Sci. U. S. A. 86 1989 1372 1376
30. S. Parthasarathy, E. Wieland, and D. Steinberg A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein Proc. Natl. Acad. Sci. U. S. A. 86 1989 1046 1050
31. S.M. Rankin, S. Parthasarathy, and D. Steinberg Evidence for a dominant role of lipoxygenase(s) in the oxidation of LDL by mouse peritoneal macrophages J. Lipid Res. 32 1991 449 456
32. C. Smith, M. Mitchinson, O.I Aruoma, and B. Halliwell Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherosclerotic lesions Biochem. J. 286 1992 901 905
33. C.P. Sparrow, T.W. Doebber, J. Olszewski, M.S. Wu, J. Ventre, K.A. Stevens, and Y.S. Chao Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the antioxidant N,N′-diphenyl-phenylenediamine J. Clin. Invest. 89 1992 1885 1891
34. D. Steinberg Clinical trials of antioxidants in atherosclerosis: are we doing the right thing? Lancet 346 1995 36 38
35. D. Steinberg, S. Parthasarathy, T.E. Carew, J.C. Khoo, and J.L. Witztum Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity N. Engl. J. Med. 320 1989 915 924
36. K. Suzumura, M. Yasuhara, K. Tanaka, and T. Suzuki Protective effect of fluvastatin sodium (XU-62-320), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on oxidative modification of human low-density lipoprotein in vitro Biochem. Pharmacol. 57 1999 697 703
37. I.B. Taraporewala, and J.M. Kauffman Synthesis and structure-activity relationships of anti-inflammatory 9,10-dihydro-9-oxo-2-acridine-alkanoic acids and 4-(2-carboxyphenyl)aminobenzenealkanoic acids J. Pharm. Sci. 79 1990 173 178
38. A.J. Vickers, and D.G. Altman Statistics notes: analysing controlled trials with baseline and follow up measurements Br. Med. J. 323 2001 1123 1124
39. R.B. Wilson, C.C. Middleton, and G.Y. Sun Vitamin E, antioxidants and lipid peroxidation in experimental atherosclerosis of rabbits J. Nutr. 108 1978 1858 1867
40. J.L. Witztum, and D. Steinberg The oxidative modification hypothesis of atherosclerosis: does it hold for humans? Trends Cardiovasc. Med. 11 2001 93 102
41. S. Yla-Herttuala, W. Palinski, M.E. Rosenfeld, S. Parthasarathy, T.E. Carew, S. Butler, J.L. Witztum, and D. Steinberg Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man J. Clin. Invest. 84 1989 1086 1095