Effect of probucol on the lipid composition of blood plasma, erythrocyte ghosts and liver membranes in mice
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Catabolism
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The effect and safety of a new cholesterol- lowering drug, probucol, was investigated in 49 hypercholesterolemia patients in Kyushu multicentral cooperative study (10 hospitals). The patients were allocated to either 750mg or 1000mg per day for 16 weeks. Both doses of probucol lowered serum cholesterol, LDL-cholesterol and HDL-cholesterol and phospholipid significantly without influencing on serum tryglyceride levels. No relationship among two doses of probucol and the degree of cholesterol lowering have been found in this study. And at all doses employed, the drug was well tolerated and no changes attributable to therapy were observed in the laboratory parameters evaluated.
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Background: Despite beneficial cholesterol‐lowering and antioxidant properties of probucol, it paradoxically increases coronary atherogenesis in apo E‐KO mice. The aim of this study was to investigate the effects of probucol on cardiac function in apo E‐KO mice. Materials and Methods: Male apo E‐KO and C57BL/6 mice were fed an atherogenic diet with (treated, n=8) or without (control, n=8) 1% probucol for 16 weeks. Plasma cholesterol levels were measured. Murine echocardiography was performed serially at 6 week intervals. Results: Probucol treatment resulted in significant reductions in plasma cholesterol levels in both apo E‐KO (−30%, p<0.05) and C57BL/6 mice (−90%, p<0.01). Apo E‐KO mice treated with probucol showed early regional LV systolic dysfunction as early as 6 weeks with further decrease over time [endocardial velocity −40%; strain −40%, ejection fraction −10% (p<0.01)], with no impact on mortality. Such effects of probucol were not observed in C57BL/6 mice. Conclusions: Probucol impairs cardiac function in apo E‐KO mice. This may be related to previously observed coronary atherogenesis due to probucol in this animal model. Supported in part by URGP, HSF and NSERC.
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Probucol
Low-density lipoprotein
Scavenger
Free radical scavenger
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Probucol, a serum cholesterol-lowering agent, was studied in a double-blind, placebo-controlled trial for one year in 118 hypercholesterolemic men. The mean decrease in the level of serum cholesterol in the probucol group (N = 88) from baseline for months 6 through 12 ranged from 16.2% to 20.9%. The mean decrease from baseline for the placebo-treated patients (N = 30) ranged from 5.2% to 12.7%. The difference between the groups was highly significant. At the end of this one-year trial, 61 of the probucol-treated patients continued receiving therapy in an open trial for up to seven years. After the second year of probucol treatment, the reduction in serum cholesterol levels ranged from 23.1% to 27.4% and was subsequently maintained. The present report shows that probucol is safe and effective for the long-term lowering of serum cholesterol levels in patients with primary hypercholesterolemia.
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OBJECTIVE To extract the sphingomyelin from erythrocyte membrane and hydrolyze it to ceramide. METHOD Sphingomyelin was prepared through the process of separating erythrocyte from blood,erythrocytolysis,dehydration,dry,et al,and then hydrolyzed to ceramide by phospholipase C. RESULTS The sphingomyelin was obtained from erythrocyte membrane with this method and the ceramide was consequently obtained. CONCLUSION Sphingomyelin can be obtained from erythrocyte membrane by this method.
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Mice were maintained under conditions of light from 7 a.m. to 7 p.m. and dark from 7 p.m. to 7 a.m. Probucol was given orally to these animals once daily at 10 a.m. or 10 p.m. for 7 days. Blood samples for serum cholesterol were obtained at 24 hours after the final dosage. Blood samples for plasma probucol were obtained just before and at 3, 6, 12, 24, 48, 72, 96 and 120 hours after the final dosage. The cholesterol lowering effect of the agent at 10 p.m. was greater than that at 10 a.m. Plasma probucol concentrations of the two trials did not differ at any observation point. These data suggest that the effect of probucol varies with its time of administration. This might not be caused by a time-dependent change in plasma probucol concentration.
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We studied the effects of administering probucol on the catabolism of low density lipoprotein (LDL) in guinea pigs. Probucol administration significantly lowered the levels of total and LDL-cholesterol in animals given either normal chow or the high cholesterol (1% W/W) diet. High-density lipoprotein cholesterol was decreased significantly in the animals fed cholesterol, but not normal chow diet. Triglyceride levels were unaffected in both groups. No significant changes were observed in the LDL receptor-dependent and LDL receptor-independent catabolism of native LDL and LDL obtained from a probucol-treated patient. However, when the LDL isolated from a probucol-treated patient was injected, the fractional catabolic rate was significantly lower than that of injected native LDL. This study indicates that probucol lowered the plasma LDL cholesterol level neither by an increased catabolism of LDL via an LDL receptor nor an LDL receptor-independent pathway.
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Catabolism
Low-density lipoprotein
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