Did we abandon probucol too soon?

Current Opinion in Lipidology

Volumn 26, Issue 4, 2015, Pages 304-316

  Yamashita, Shizuya ^a,b   Masuda, Daisaku ^b   Matsuzawa, Yuji ^c  

^a Department of Community Medicine ^*  (Japan)

^b OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^c SUMITOMO HOSPITAL   (Japan)

Author keywords

Cholesteryl ester transfer protein; HDL; probucol; reverse cholesterol transport; xanthoms

Indexed keywords

ANTIOXIDANT; ARYLDIALKYLPHOSPHATASE 1; CHOLESTEROL ESTER TRANSFER PROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; PROBUCOL; SCAVENGER RECEPTOR BI; CHOLESTEROL;

ANTIDIABETIC ACTIVITY; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR MORTALITY; CAROTID ARTERY; CAROTID ATHEROSCLEROSIS; CHOLESTEROL TRANSPORT; CHRONIC KIDNEY DISEASE; CORONARY ARTERY ATHEROSCLEROSIS; DRUG MECHANISM; ENZYME ACTIVITY; FAMILIAL HYPERCHOLESTEROLEMIA; FEMORAL ARTERY; FEMORAL ATHEROSCLEROSIS; HEART MUSCLE REVASCULARIZATION; HEART PROTECTION; HUMAN; KIDNEY INJURY; LIPID METABOLISM; MULTICENTER STUDY (TOPIC); NONALCOHOLIC FATTY LIVER; NONHUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESTENOSIS; REVIEW; SECONDARY PREVENTION; XANTHOMA; ANIMAL; CARDIOVASCULAR SYSTEM; CHEMISTRY; DRUG EFFECTS; METABOLISM; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; CARDIOVASCULAR SYSTEM; CHOLESTEROL; HUMANS; PROBUCOL;

EID: 84941342079     PISSN: 09579672     EISSN: 14736535     Source Type: Journal    
DOI: 10.1097/MOL.0000000000000199     Document Type: Review

References (110)

1. Cholesterol Treatment Trialists' (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomized trials-prospective meta-analysis of data. Lancet 2012; 380:581-590.
2. Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174 000 participants in 27 randomised trials. Lancet 2015; 385:1397-1405.
3. Expert Dyslipidemia Panel of the International Atherosclerosis Society Panel members. An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia-full report. J Clin Lipidol 2014; 8:29-60.
4. Stone NJ, Robinson JG, Lichtenstein AH, et al., American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129 (25 Suppl 2):S1-S45.
5. The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2011; 32:1769-1818.
6. Superko HR, King S 3rd. Lipid management to reduce cardiovascular risk: a new strategy is required. Circulation 2008; 117:560-568.
7. Barnhart JW, Sefranka JA, McIntosh DD. Hypocholesterolemic effect of 4,4'-(isopropylidenedithio)-bis(2,6-di-t-butylphenol) (probucol). Am J Clin Nutr 1970; 23:1229-1233.
8. Urien S, Riant P, Albengres E, et al. In vitro studies on the distribution of probucol among human plasma lipoproteins. Mol Pharmacol 1984; 26:322-327.
9. Buckley MM, Goa KL, Price AH, et al. Probucol A reappraisal of its pharmacological properties and therapeutic use in hypercholesterolaemia. Drugs 1989; 37:761-800.
10. Tawara K, Tomikawa M, Abiko Y. Mode of action of probucol in reducing serum cholesterol in mice. Jpn J Pharmacol 1986; 40:123-133.
11. Naruszewicz M, Carew TE, Pittman RC, et al. A novel mechanism by which probucol lowers low density lipoprotein levels demonstrated in the LDL receptor-deficient rabbit. J Lipid Res 1984; 25:1206-1213.
12. Baker SG, Joffe BI, Mendelsohn D, et al. Treatment of homozygous familial hypercholesterolaemia with probucol. S Afr Med J 1982; 62:7-11.
13. Matsuzawa Y, Yamashita S, Funahashi T, et al. Selective reduction of cholesterol in HDL2 fraction by probucol in familial hypercholesterolemia and hyperHDL2 cholesterolemia with abnormal cholesteryl ester transfer. Am J Cardiol 1988; 62:66B-72B.
14. Durrington PN, Miller JP. Double-blind, placebo-controlled, cross-over trial of probucol in heterozygous familial hypercholesterolaemia. Atherosclerosis 1985; 55:187-194.
15. Sanjurjo P, Martul P, Sasieta M, et al. Treatment with probucol of children with familial hypercholesterolaemia. Acta Paediatr Scand 1988; 77:132-135.
16. Cristol LS, Jialal I, Grundy SM. Effect of low-dose probucol therapy on LDL oxidation and the plasma lipoprotein profile in male volunteers. Atherosclerosis 1992; 97:11-20.
17. Kaminnyi AI, Lankin VZ, Perepelitsa EI, et al. Relationship between freeradical lipid oxidation and efficiency of coronary angioplasty in coronary patients. Bull Exp Biol Med 2007; 144:664-666.
18. Carew TE, Schwenke DC, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci USA 1987; 84:7725-7729.
19. Kita T, Yokode M, Ishii K, et al. The role of oxidized lipoproteins in the pathogenesis of atherosclerosis. Clin Exp Pharmacol Physiol Suppl 1992; 20:37-42.
20. Brasen JH, Koenig K, Bach H, et al. Comparison of the effects of alphatocopherol, ubiquinone-10 and probucol at therapeutic doses on atherosclerosis in WHHL rabbits. Atherosclerosis 2002; 163:249-259.
21. Hoshida S, Yamashita N, Igarashi J, et al. Long-term probucol treatment reverses the severity of myocardial injury in Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol 1997; 17:2801-2807.
22. Fruebis J, Gonzalez V, Silvestre M, et al. Effect of probucol treatment on gene expression of VCAM-1, MCP-1, and M-CSF in the aortic wall of LDL receptor-deficient rabbits during early atherogenesis. Arterioscler Thromb Vasc Biol 1997; 17:1289-1302.
23. Zapolska-Downar D, Zapolski-Downar A, Markiewski M, et al. Selective inhibition by probucol of vascular cell adhesion molecule-1 (VCAM-1) expression in human vascular endothelial cells. Atherosclerosis 2001; 155:123-130.
24. Deng YM, Wu BJ, Witting PK, et al. Probucol protects against smooth muscle cell proliferation by up-regulating heme oxygenase-1. Circulation 2004; 110:1855-1860.
25. Heinecke JW. Lipoprotein oxidation in cardiovascular disease: chief culprit or innocent bystander? J Exp Med 2006; 203:813-816.
26. Jiang JL, Li NS, Li YJ, et al. Probucol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level. Br J Pharmacol 2002; 135:1175-1182.
27. Jiang JL, Zhang XH, Li NS, et al. Probucol decreases asymmetrical dimethylarginine level by alternation of protein arginine methyltransferase I and dimethylarginine dimethylaminohydrolase activity. Cardiovasc Drugs Ther 2006; 20:281-294.
28. Noto H, Kawamura M, Hashimoto Y, et al. Modulation of HDL metabolism by probucol in complete cholesteryl ester transfer protein deficiency. Atherosclerosis 2003; 171:131-136.
29. Hong SC, Zhao SP, Wu ZH. Probucol up-regulates paraoxonase 1 expression in hepatocytes of hypercholesterolemic rabbits. J Cardiovasc Pharmacol 2006; 47:77-81.
30. McPherson R, Hogue M, Milne RW, et al. Increase in plasma cholesteryl ester transfer protein during probucol treatment. Relation to changes in high density lipoprotein composition. Arterioscler Thromb 1991; 11:476-481.
31. Chiesa G, Michelagnoli S, Cassinotti M, et al. Mechanisms of high-density lipoprotein reduction after probucol treatment: changes in plasma cholesterol esterification/transfer and lipase activities. Metabolism 1993; 42:229-235.
32. Ishigami M, Yamashita S, Sakai N, et al. High-density lipoproteins from probucol-treated patients have increased capacity to promote cholesterol efflux from mouse peritoneal macrophages loaded with acetylated lowdensity lipoproteins. Eur J Clin Invest 1997; 27:285-292.
33. Adlouni A, El Messal M, Saile R, et al. Probucol promotes reverse cholesterol transport in heterozygous familial hypercholesterolemia. Effects on apolipoprotein AI-containing lipoprotein particles. Atherosclerosis 2000; 152:433-440.
34. Rinninger F, Wang N, Ramakrishnan R, et al. Probucol enhances selective uptake of HDL-associated cholesteryl esters in vitro by a scavenger receptor B-I-dependent mechanism. Arterioscler Thromb Vasc Biol 1999; 19:1325-1332.
35. Hirano K, Ikegami C, Tsujii K, et al. Probucol enhances the expression of human hepatic scavenger receptor class B type I, possibly through a species-specific mechanism. Arterioscler Thromb Vasc Biol 2005; 25:2422-2427.
36. Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007; 357:2109-2122.
37. Kastelein JJ, van Leuven SI, Burgess L, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med 2007; 356:1620-1630.
38. Schwartz GG,Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012; 367:2089-2099.
39. Matsuzawa Y, Yamashita S, Kameda K, et al. Marked hyper-HDL2-cholesterolemia associated with premature corneal opacity. A case report. Atherosclerosis 1984; 53:207-212.
40. Zhong S, Sharp DS, Grove JS, et al. Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL Levels. J Clin Invest 1996; 97:2917-2923.
41. Hirano K, Yamashita S, Nakajima N, et al. Genetic cholesteryl ester transfer protein deficiency is extremely frequent in the Omagari area of Japan. Marked hyperalphalipoproteinemia caused by CETP gene mutation is not associated with longevity. Arterioscler Thromb Vasc Biol 1997; 17:1053-1059.
42. Robins SJ, Lyass A, Brocia RW, et al. Plasma lipid transfer proteins and cardiovascular disease. The Framingham Heart Study. Atherosclerosis 2013; 228:230-236.
43. Ritsch A, Scharnagl H, Eller P, et al. Cholesteryl ester transfer protein and mortality in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health study. Circulation 2010; 121:366-374.
44. Yamamoto A, Matsuzawa Y, Yokoyama S, et al. Effects of probucol on xanthomata regression in familial hypercholesterolemia. Am J Cardiol 1986; 57:29H-35H.
45. Fujita M, Shirai K. A comparative study of the therapeutic effect of probucol and pravastatin on xanthelasma. J Dermatol 1996; 23:598-602.
46. Yamamoto A, Hara H, Takaichi S, et al. Effect of probucol on macrophages, leading to regression of xanthomas and atheromatous vascular lesions. Am J Cardiol 1988; 62:31B-36B.
47. Miida T, Seino U, Miyazaki O, et al. Probucol markedly reduces HDL phospholipids and elevated prebeta1-HDL without delayed conversion into alpha-migrating HDL: putative role of angiopoietin-like protein 3 in probucolinduced HDL remodeling. Atherosclerosis 2008; 200:329-335.
48. Favari E, Zanotti I, Zimetti F, et al. Probucol inhibits ABCA1-mediated cellular lipid efflux. Arterioscler Thromb Vasc Biol 2004; 24:2345-2350.
49. Moghadasian MH, McManus BM, Godin DV, et al. Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein Edeficient mice: possible mechanisms of action. Circulation 1999; 99:1733-1739.
50. Moghadasian MH. Dietary phytosterols reduce probucol-induced atherogenesis in apo E-KO mice. Atherosclerosis 2006; 188:28-34.
51. Kita T, Nagano Y, Yokode M, et al. Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci USA 1987; 84:5928-5931.
52. Niimi M, Keyamura Y, Nozako M, et al. Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits. Lipids Health Dis 2013; 12:166.
53. Li S, Liang J, Niimi M, et al. Probucol suppresses macrophage infiltration and MMP expression in atherosclerotic plaques of WHHL rabbits. J Atheroscler Thromb 2014; 21:648-658.
54. Sheng L, Shao L, Bi S, et al. Probucol inhibits hydrogen peroxide to induce apoptosis of vascular smooth muscle cells. Mol Med Rep 2013; 7:1185-1190.
55. Li T, Chen W, An F, et al. Probucol attenuates inflammation and increases stability of vulnerable atherosclerotic plaques in rabbits. Tohoku J Exp Med 2011; 225:23-34.
56. Keyamura Y, Nagano C, Kohashi M, et al. Add-on effect of probucol in atherosclerotic, cholesterol-fed rabbits treated with atorvastatin. PLOS One 2014; 9:e96929.
57. Braun A, Zhang S, Miettinen HE, et al. Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse. Proc Natl Acad Sci USA 2003; 100:7283-7288.
58. Miida T, Yamaguchi T, Tsuda T, et al. High prebeta1-HDL levels in hypercholesterolemia are maintained by probucol but reduced by a low-cholesterol diet. Atherosclerosis 1998; 138:129-134.
59. Smith JD. Dysfunctional HDL as a diagnostic and therapeutic target. Arterioscler Thromb Vasc Biol 2010; 30:151-155.
60. Inagaki M, Nakagawa-Toyama Y, Nishida M, et al. Effect of probucol on antioxidant properties of HDL in patients with heterozygous familial hypercholesterolemia. J Atheroscler Thromb 2012; 19:643-656.
61. Hong SC, Zhao SP,WuZH. Effect of probucol on HDL metabolism and class B type I scavenger receptor (SR-BI) expression in the liver of hypercholesterolemic rabbits. Int J Cardiol 2007; 115:29-35.
62. Yamamoto S, Tanigawa H, Li X, et al. Pharmacologic suppression of hepatic ATP-binding cassette transporter 1 activity in mice reduces high-density lipoprotein cholesterol levels but promotes reverse cholesterol transport. Circulation 2011; 124:1382-1390.
63. Zhong JK, Guo ZG, Li C, et al. Probucol alleviates atherosclerosis and improves high density lipoprotein function. Lipids Health Dis 2011; 10:210.
64. Walldius G, Carlson LA, Erikson U, et al. Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST)-a status report. Am J Cardiol 1988; 62:37B-43B.
65. Walldius G, Erikson U, Olsson AG, et al. The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST). Am J Cardiol 1994; 74:875-883.
66. Gallino A, Do DD, Alerci M, et al. Effects of probucol versus aspirin and versus brachytherapy on restenosis after femoropopliteal angioplasty: the PAB randomized multicenter trial. J Endovasc Ther 2004; 11:595-604.
67. Sawayama Y, Shimizu C, Maeda N, et al. Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST). J Am Coll Cardiol 2002; 39:610-616.
68. Ko YG, Kim BK, Lee BK, et al. Study design and rationale of "Synergistic effect of combination therapy with cilostazol and ProbUcol on plaque stabilization and lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial. Trials 2011; 12:10.
69. Ko YG, Choi SH, Kang WC, et al. Effects of combination therapy with cilostazol and probucol versus monotherapy with cilostazol on coronary plaque, lipid and biomarkers: SECURE study, a double-blind randomized controlled clinical trial. J Atheroscler Thromb 2014; 21:816-830.
70. Anderson TJ, Meredith IT, Yeung AC, et al. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med 1995; 332:488-493.
71. Yamashita S, Bujo H, Arai H, et al. Long-term probucol treatment prevents secondary cardiovascular events: a cohort study of patients with heterozygous familial hypercholesterolemia in Japan. J Atheroscler Thromb 2008; 15:292-303.
72. Kasai T, Miyauchi K, Kubota N, et al. Probucol therapy improves long-term (>10-year) survival after complete revascularization: a propensity analysis. Atherosclerosis 2012; 220:463-469.
73. Setsuda M, Inden M, Hiraoka N, et al. Probucol therapy in the prevention of restenosis after successful percutaneous transluminal coronary angioplasty. Clin Ther 1993; 15:374-382.
74. Tardif JC, Cote G, Lesperance J, et al. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. Multivitamins and Probucol Study Group. N Engl J Med 1997; 337:365-372.
75. Cô té G, Tardif JC, Lespé rance J, et al. Effects of probucol on vascular remodeling after coronary angioplasty. Multivitamins and Protocol Study Group. Circulation 1999; 99:30-35.
76. Yokoi H, Daida H, Kuwabara Y, et al. Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial. J Am Coll Cardiol 1997; 30:855-862.
77. Daida H, Kuwabara Y, Yokoi H, et al. Effect of probucol on repeat revascularization rate after percutaneous transluminal coronary angioplasty (from the Probucol Angioplasty Restenosis Trial [PART]). Am J Cardiol 2000; 86:550-552.
78. Sekiya M, Funada J, Watanabe K, et al. Effects of probucol and cilostazol alone and in combination on frequency of poststenting restenosis. Am J Cardiol 1998; 82:144-147.
79. Kim MH, Cha KS, Han JY, et al. Effect of antioxidant probucol for preventing stent restenosis. Catheter Cardiovasc Interv 2002; 57:424-428.
80. Tardif JC, Gregoire J, Schwartz L, et al. Effects of AGI-1067 and probucol after percutaneous coronary interventions. Circulation 2003; 107:552-558.
81. Tardif JC, Gré goire J, L'Allier PL, et al. Effects of the antioxidant succinobucol (AGI-1067) on human atherosclerosis in a randomized clinical trial. Atherosclerosis 2008; 197:480-486.
82. Nunes GL, Abizaid AC, Theodoro MO, et al. Role of probucol in inhibiting intimal hyperplasia after coronary stent implantation: a randomized study. Am Heart J 2006; 152:914e1-914e7.
83. Stocker R. Molecular mechanisms underlying the antiatherosclerotic and antidiabetic effects of probucol, succinobucol, and other probucol analogues. Curr Opin Lipidol 2009; 20:227-235.
84. Dussault S, Dhahri W, Desjarlais M, et al. Elsibucol inhibits atherosclerosis following arterial injury: multifunctional effects on cholesterol levels, oxidative stress and inflammation. Atherosclerosis 2014; 237:194-199.
85. Meng CQ, Somers PK, Rachita CL, et al. Novel phenolic antioxidants as multifunctional inhibitors of inducible VCAM-1 expression for use in atherosclerosis. Bioorg Med Chem Lett 2002; 12:2545-2548.
86. Kunsch C, Luchoomun J, Grey JY, et al. Selective inhibition of endothelial and monocyte redox-sensitive genes by AGI-1067; a novel antioxidant and antiinflammatory agent. J Pharmacol Exp Ther 2004; 308:820-829.
87. Wu BJ, Kathir K, Witting PK, et al. Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging. J Exp Med 2006; 203:1117-1127.
88. Sundell CL, Somers PK, Meng CQ, et al. AGI-1067: a multifunctional phenolic antioxidant, lipid modulator, anti-inflammatory and antiatherosclerotic agent. J Pharmacol Exp Ther 2003; 305:1116-1123.
89. Tardif JC, McMurray JJ, Klug E, et al. Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebocontrolled trial. Lancet 2008; 371:1761-1768.
90. Wu R, Zhang W, Liu B, et al. Probucol ameliorates the development of nonalcoholic steatohepatitis in rats fed high-fat diets. Dig Dis Sci 2013; 58:163-171.
91. Zhan Y-T, Weng J, Li L, et al. Protective effect of probucol on liver injury induced by carbon tetrachloride in rats. Hepatol Int 2011; 5:899-905.
92. Merat S, Malekzadeh R, Sohrabi MR, et al. Probucol in the treatment of nonalcoholic steatohepatitis: a double-blind randomized controlled study. J Hepatol 2003; 38:414-418.
93. Merat S, Aduli M, Kazemi R, et al. Liver histology changes in nonalcoholic steatohepatitis after one year of treatment with probucol. Dig Dis Sci 2008; 53:2246-2250.
94. Tokushige K, Hashimoto E, Yatsuji S, et al. Combined pantethine and probucol therapy for Japanese patients with nonalcoholic steatohepatitis. Hepatol Res 2007; 37:872-877.
95. Ishitobi T, Hyogo H, Tokumo H, et al. Efficacy of probucol for the treatment of nonalcoholic steatohepatitis with dyslipidemia: an open-label pilot study. Hepatol Res 2014; 44:429-435.
96. Hirano T, Morohoshi T. Treatment of hyperlipidemia with probucol suppresses the development of focal and segmental glomerulosclerosis in chronic aminonucleoside nephrosis. Nephron 1992; 60:443-447.
97. Binder CJ, Weiher H, Exner M, et al. Glomerular overproduction of oxygen radicals in Mpv17 gene-inactivated mice causes podocyte foot process flattening and proteinuria: a model of steroid-resistant nephrosis sensitive to radical scavenger therapy. Am J Pathol 1999; 154:1067-1075.
98. Nagao S, Yamaguchi T, Kasahara M, et al. Effect of probucol in a murine model of slowly progressive polycystic kidney disease. Am J Kidney Dis 2000; 35:221-226.
99. Koya D, Hayashi K, Kitada M, et al. Effects of antioxidants in diabetes-induced oxidative stress in the glomeruli of diabetic rats. J Am Soc Nephrol 2003; 14 (8 Suppl 3):S250-S253.
100. Zhou G, Wang Y, He P, et al. Probucol inhibited Nox2 expression and attenuated podocyte injury in type 2 diabetic nephropathy of db/db mice. Biol Pharm Bull 2013; 36:1883-1890.
101. Haas M, Mayer G, Wirnsberger G, et al. Antioxidant treatment of therapyresistant idiopathic membranous nephropathy with probucol: a pilot study. Wien Klin Wochenschr 2002; 114:143-147.
102. Endo K, Miyashita Y, Sasaki H, et al. Probucol delays progression of diabetic nephropathy. Diabetes Res Clin Pract 2006; 71:156-163.
103. Endo K, Saiki A, Yamaguchi T, et al. Probucol suppresses initiation of chronic hemodialysis therapy and renal dysfunction-related death in diabetic nephropathy patients: Sakura study. J Atheroscler Thromb 2013; 20:494-502.
104. Yin L, Li G, Liu T, et al. Probucol for the prevention of cystatin C-based contrast-induced acute kidney injury following primary or urgent angioplasty: a randomized, controlled trial. Int J Cardiol 2013; 167:426-429.
105. Kuyvenhoven JP, Meinders AE. Oxidative stress and diabetes mellitus. Pathogenesis of long-term complications. Eur J Intern Med 1999; 10:9-19.
106. Harada N, Kashiwagi A, Nishio Y, et al. Effects of cholesterol-lowering treatments on oxidative modification of plasma intermediate density lipoprotein plus low density lipoprotein fraction in type 2 diabetic patients. Diabetes Res Clin Pract 1999; 43:111-120.
107. Tagawa T, Urabe Y, Kimura Y, et al. Long-term treatment with probucol improves endothelial function in patients with coronary artery disease. Hypertens Res 2004; 27:311-318.
108. Chisolm GM 3rd, Morel DW. Lipoprotein oxidation and cytotoxicity: effect of probucol on streptozotocin-treated rats. Am J Cardiol 1988; 62:20B-26B.
109. Gorogawa S, Kajimoto Y, Umayahara Y, et al. Probucol preserves pancreatic beta-cell function through reduction of oxidative stress in type 2 diabetes. Diabetes Res Clin Pract 2002; 57:1-10.
110. Yamashita S,Matsuzawa Y. Where are we with probucol: a new life for an old drug? Atherosclerosis 2009; 207:16-23.