Atorvastatin and gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation

Atherosclerosis

Volumn 138, Issue 2, 1998, Pages 271-280

  Aviram, Michael ^a   Rosenblat, Mira ^a   Bisgaier, Charles L ^b   Newton, Roger S ^b  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b PFIZER INC   (United States)

Author keywords

Atorvastatin; Gemfibrozil; HDL; LDL; Lipid proxidation; Paraoxonase; VLDL

Indexed keywords

2,2' AZOBIS(2 AMIDINOPROPANE); ANTIOXIDANT; ARYLESTERASE; ATORVASTATIN; COPPER SULFATE; DRUG METABOLITE; GEMFIBROZIL; HIGH DENSITY LIPOPROTEIN; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; SCAVENGER; VERY LOW DENSITY LIPOPROTEIN;

ARTICLE; CHELATION; HUMAN; LIPID PEROXIDATION; MACROPHAGE; PRIORITY JOURNAL;

ANTILIPEMIC AGENTS; ANTIOXIDANTS; GEMFIBROZIL; HEPTANOIC ACIDS; HUMANS; LIPID PEROXIDATION; LIPOPROTEINS, LDL; PYRROLES;

EID: 0032103277     PISSN: 00219150     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0021-9150(98)00032-X     Document Type: Article

References (54)

1. Steinberg D., Parthasarathy S., Carew T.E., Khoo J.C., Witztum J.L. Beyond cholesterol: modificatins of low-density lipoprotein that increase its atherogenicity. New Engl J Med. 320:1989;915-924.
2. Berliner J.A., Navab M., Fogelman A.M.et al. Atherosclerosis: basic mechanisms oxidation, inflammation and genetics. Circulation. 91:1995;2488-2496.
3. Aviram M. Oxidative modification of low density lipoprotein and its relation to atherosclerosis. Isr J Med Sci. 31:1995;241-249.
4. Parthasarathy S., Quinn M.T., Schwenke D.C., Carew T.E., Steinberg D. Oxidative modification of β-very low density lipoprotein. Potential role in monocyte recruitment and foam cell formation. Arteriosclerosis. 9:1989;398-404.
5. Keidar S., Kaplan M., Rosenblat M., Brook J.G., Aviram M. Apolipoprotein E and lipoprotein lipase reduce macrophage degradation of oxidized very-low density lipoprotein (VLDL), but increase cellular degradation of native VLDL. Metabolism. 41:1992;1185-1192.
6. Kita T., Yokode M., Ishii K.et al. The role of oxidized lipoproteins in the pathogenesis of atherosclerosis. Clin Exp Pharmacol Physiol Suppl. 20:1992;37-42.
7. Nagano Y., Arai H., Kita T. High density lipoprotein loses its effect to stimulative efflux of cholesterol from foam cells after oxidative modification. Proc Natl Acad Sci USA. 88:1991;6457-6461.
8. Esterbauer H., Dieber-Rotheneder M., Striegl G., Waeg G. Role of vitamin E in preventing the oxidation of low-density lipoprotein. Am J Clin Nutr. 53(1):1991;314S-321S.
9. Lavy A., Ben Amotz A., Aviram M. Preferential inhibition of LDL oxidation by the all-trans isomer of -carotene in comparison to the 9-cis-carotene. Eur J Clin Chem Clin Biochem. 31:1993;83-90.
10. Fuhrman B, Ben-Yaish L, Attias J, Hayek T, Aviram M. Tomato's lycopene and β-carotene inhibit low density lipoprotein oxidation and this effect depends on the lipoprotein vitamin E content. Nutr Metab Cardiovas Dis 1997;7:433-38.
11. Fuhrman B., Lavy A., Aviram M. Dietary supplementation of red wine reduces the susceptibility of human plasma and LDL to undergo lipid peroxidation. Am J Clin Nutr. 61:1995;549-554.
12. Hayek T, Fuhrman B, Vaya J et al. Reduced progression of atherosclerosis in the apolipoprotein E deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and to aggregation. Arterioscler. Thromb Vasc Biol 1997;17:2744-52.
13. Navab M., Berliner J.A., Watson A.D.et al. The ying and yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol. 16:1996;831-842.
14. Lavy A., Brook J.G., Dankner G., Ben Amotz A., Aviram M. Enhanced in vitro oxidation of plasma lipoproteins derived from hypercholesterolemic patients. Metabolism. 40:1991;794-799.
15. Aviram M., Keidar S., Brook J.G. Dual effect of lovastatin and simvastatin on LDL-macrophage interaction. Eur J Clin Chem Clin Biochem. 29:1991;657-664.
16. Aviram M., Dankner G., Cogan U., Hochgraf E., Brook J.G. Lovastatin inhibits low-density lipoprotein oxidation and alters its fluidity and uptake by macrophages: in vitro and in vivo studies. Metabolism. 41:1992;229-235.
17. Hoffman R., Brook J.G., Aviram M. Hypolipidemic drugs reduce lipoprotein susceptibility to undergo lipid peroxidation: in vitro and ex vivo studies. Atherosclerosis. 93:1992;105-113.
18. Hussein O., Schlesinger S., Rosenblat M., Keidar S., Aviram M. Reduced susceptibility of 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. Giroux L.M., Davignon J., Naruszewicz M. Simvastatin inhibits the oxidation of low-density lipoproteins by activated human monocyte-derived macrophages. Biochim Biophys Acta. 1165:1993;335-338.
20. Aviram M. Oxidized low density lipoprotein (ox-LDL) interaction with macrophages in atherosclerosis and the antiatherogenicity of antioxidants. Eur J Clin Chem Clin Biochem. 34:1996;599-608.
21. Huff M.W. Fibrates and HMG-CoA reductase inhibitors. Can Med Assoc J. 145:1991;977-987.
22. Davignon J. Atorvastatin: a statin with a large spectrum of action. Atherosclerosis. 2:1997;243-252.
23. Duggan D.E., Vickers S. Physiological disposition of HMG-CoA-reductase inhibitors. Drug Metabol Rev. 22:1990;333-362.
24. Bakker-Arkema R.G., Davidson M.H., Goldstein R.J.et al. Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia. JAMA. 275:1996;128-133.
25. Nawrocki J.W., Weiss S.R., Davidson M.H.et al. Reduction of LDL cholesterol by 25 to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor. Arterioscler Thromb Vasc Biol. 15:1995;678-682.
26. Auerbach B.J., Krause B.R., Bisgaier C.L., Newton R.S. Comparative effects of HMG-CoA reductase inhibitors on apo B production in the casein-fed rabbit: atorvastatin versus lovastatin. Atherosclerosis. 115:1995;173-180.
27. Krause B.R., Newton R.S. Lipid-lowering activity of atorvastatin and lovastatin in rodent species: triglyceride-lowering in rats correlates with efficacy in LDL animal models. Atherosclerosis. 117:1995;237-244.
28. Radulovic L.L., Cilla D.D., Posvar E.L., Sedman A.J., Whitfield L.R. Effect of food on the bioavailability of atorvastatin, an HMG-CoA reductase inhibitor. J Clin Pharmacol. 35:1995;990-994.
29. Posvar E.L., Radulvoic L.L., Cilla D.D. Jr., Whitfield L.R., Sedman A.J. Tolerance and pharmacokinetics of single-dose atorvastatin,a potent inhibitor of HMG-CoA reductase, in healthy subjects. J Clin Pharmacol. 36:1996;728-731.
30. Cilla D.D. Jr., Whitfield L.R., Gibson D.M., Sedman A.J., Posvar E.L. Multiple-dose pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an inhibitor of HMG-CoA reductase in healthy subjects. Clin Pharmacol Ther. 60:1996;687-695.
31. Grundy S.M., Vega G.L. Fibric acids: effects on lipids and lipoprotein metabolism. Am J Med. 83:1987;9-20.
32. Haubenwallner S., Essenburg A.D., Barnet B.C.et al. Hypolipidemic activity of select fibrates correlates to changes in hepatic apolipoprotein C-III expression: a potential physiologic basis for their mode of action. J Lipid Res. 36:1995;2541-2551.
33. Hertz R., Bishara-Shieban J., Bar-Tana J. Mode of action of peroxisome proliferators as hypolipidemic drugs. Suppression of apolipoprotein C-III. J Biol Chem. 270:1995;13470-13475.
34. Staels B., Vu-Dac N., Kosykh V.A.et al. Fibrates downregulate apolioprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates. J Clin Invest. 95:1995;705-712.
35. Berthou L., Saladin R., Yaqoob P.et al. Regulation of rat liver apolipoprotein A-I, apolipoprotein A-II and acyl-coenzyme A oxidase gene expression by fibrates and dietary fatty acids. Eur J Biochem. 232:1995;179-187.
36. Frick M.H., Elo O., Haapa K.et al. Primary-prevention trial with gemfibrozil in middle aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. New Engl J Med. 317:1987;1237-1245.
37. Kahri J., Sane T., van Tol A., Taskinen M.R. Effect of gemfibrozil on the regulation of HDL subfractions in hypertriglyceridemic patients. J Intern Med. 238:1995;429-436.
38. Ramharck R., Spahr M.A., Hicks G.W.et al. Gemfibrozil significantly lowers cynomolgus monkey plasma lipopprotein(a)-protein and liver apolipoprotein(a) mRNA levels. J Lipid Res. 36:1995;1294-1304.
39. Sallustio B.C., Fairchild B.A. Biosynthesis, characterisation and direct high-performance liquid chromatographic analysis of gemfibrozil 1-O-β-acylglucuronide. J Chromatogr B Biomed Appl. 665:1995;345-353.
40. Sallustio B.C., Foster D.J. Reactivity of gemfibrozil 1-o-β-acyl glucuronide. Pharmacokinetics of covalently bound gemfibrozil-protein adducts in rats. Drug Metab Dispos. 23:1995;892-899.
41. Aviram M. Plasma lipoprotein separation by discontinuous density gradient ultracentrifugation in hyperlipoproteinemic patients. Biochem Med. 30:1983;111-118.
42. Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.S. Protein measurement with the folin phenol reagent. J Biol Chem. 193:1951;65-275.
43. Frei B., Stocker R., Ames B.N. Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci USA. 85:1988;9748-9752.
44. Buege J.A., Aust S.D. Microsomal lipid peroxidation. Methods Enzymol. 52:1978;302-310.
45. El-Sadani M., Esterbauer H., El-Sayed M., Goher M., Nassar A.Y., Jurgens G. A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent. J Lipid Res. 30:1989;627-630.
46. Esterbauer H., Striegl G., Puhl H., Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun. 6:1989;67-75.
47. Blois M.S. Antioxidant determination by the use of a stable free radical. Nature. 181:1958;1199-1200.
48. Gan K.N., Smolen A., Eckerson H.W., La Du B.N. Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos. 19:1991;100-106.
49. Reaven P.D., Witztum J.L Oxidized low density lipoproteins in atherogenesis: role of dietary modification. Annu Rev Nutr. 16:1996;51-71.
50. Regnstrom J., Nilsson J. Lipid oxidation and inflammation-induced intimal fibrosis in coronary heart disease. J Lab Clin Med. 124:1994;162-168.
51. Kiechl S., Aichner F., Gerstenbrand F.et al. Body iron stores and presence of carotid atherosclerosis. Results from the Bruneck study. Arterioscler Thromb. 14:1994;1625-1630.
52. Bredie S.J., de Bruin T.W., Demacker P.N., Kastelein J.J., Stalenhoef A.F. Comparison of gemfibrozil versus simvastatin in familial combined hyperlipidemia and effects on apolipoprotein-B-containing lipoproteins, low-density lipoprotein subfraction profile, and low-density lipoprotein oxidizability. Am J Cardiol. 75:1995;348-353.
53. La Du B.N. Structural and functional diversity of paraoxonases. Nat Med. 2:1996;1186-1187.
54. Mackness M., Mackness B., Durrington P.N., Connelly P.W., Hegele R.A. Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Curr Opin Lipidol. 7:1996;69-76.