Serum Lipoprotein Metabolism Research Articles

Effects of triamcinolone on brain and cerebrospinal fluid apolipoprotein E levels in rats

The effects of the short term administration of triamcinolone (0.5 mg per 100 g body weight, 5 days) on apolipoprotein E and A-I concentrations in cerebrospinal fulid (CSF), brain extract and serum were studied in male Wistar rats using enzyme immunoassays. ApoE was significantly increased by triamcinolone in apoE-rich HDL1 in serum; 40 ± 13 (mean ± SD) vs. 68 ± 23 mg dl (15 saline-treated rats vs. 11 triamcinolone-treated rats)(P < 0.01), which was paralleled by an increase in serum apoA-I (76 ± 21 vs. 184 ± 24 mg dl ), while serum lipids also increased significantly. No significant difference was observed in the apoE concentrations in CSF (296 ± 170 vs. 269 ± 67 μg dl ) or brain extract (5.0 ± 1.6 vs. 5.7 ± 1.8 μg g wet weight). The apoA-I concentrations found in CSF and brain extract were much lower than those for apoE and were not appreciably affected by triamcinolone: 7.7 ± 5.5 vs. 4.5 ± 3.1 μg dl for CSF and < 0.5 vs. < 0.5 μg g wet weight for brain extract. The apo E metabolism in the rat central nervous system appears to be refractory to the short term administration of triamcinolone and to changes in the serum lipoprotein metabolism. ApoA-I appears unlikely to play a significant role in the rat central nervous system.

Children with cerebrotendinous xanthomatosis: clinical spectrum and response to treatment

Treatments by oral administration of chenodeoxycholic acid (CDCA) alone, 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitor (pravastatin) alone, and combination of the two drugs were attempted for 7 patients with cerebrotendinous xanthomatosis (CTX). CDCA treatment at a dose of 300 mg/day reduced serum cholestanol (67.3% reduction), lathosterol (50.8%), campesterol (61.7%) and sitosterol (12.7%). However, the sera of the patients changed to be “atherogenic”; total cholesterol, triglyceride and low-density lipoprotein (LDL)-cholesterol were increased, while high-density lipoprotein (HDL)-cholesterol was decreased. Contrarily, pravastatin at a dose of 10 mg/day improved the sera of the patients to be markedly “anti-atherogenic”, but the reductions of cholestanol (30.4%), lathosterol (44.0%), campesterol (22.9%) and sitosterol (9.6%) were inadequate. Combined treatment with CDCA and pravastatin showed good overlapping of the effects of each drug alone. The sera of the patients were apparently more “anti-atherogenic” than those after CDCA treatment. Serum cholestanol concentration was still 2.7 times higher than in controls, but the serum lathosterol level was within the normal range, indicating that the enhancement of overall cholesterol synthesis in the patients was sufficiently suppressed. Plant sterol levels were also within the normal range. The combination of CDCA and pravastatin was a good treatment for CTX, based on the improvement of serum lipoprotein metabolism, the suppression of cholesterol synthesis, and reductions of cholestanol and plant sterol levels. In all of 7 patients, the progression of disease was arrested, but dramatic effects on clinical manifestations, xanthoma, and electrophysiological findings could not be found after the treatment of these drugs.

SESAME LIGNANS MODULATE CHOLESTEROL METABOLISM IN THE STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RAT

1. Effects of sesamin and episesamin (an epimer of sesamin) on lipid metabolism, in particular cholesterol metabolism, were examined in normocholesterolaemic and hypercholesterolaemic stroke-prone spontaneously hypertensive rats (SHRSP). 2. In normocholesterolaemic SHRSP fed a regular diet, both sesamin and episesamin significantly increased the concentration of serum total cholesterol, which was due to an increase of high density lipoprotein (HDL) subfraction rich in apoE (apoE-HDL). In addition, both substances effectively decreased serum very low density lipoprotein (VLDL). In the liver, only episesamin significantly decreased the activity of microsomal acyl-CoA:cholesterol acyltransferase. 3. In hypercholesterolaemic SHRSP fed a high-fat and high-cholesterol diet (HFC diet), only episesamin improved serum lipoprotein metabolism with an increase in apoA-I and a decrease in apoB. In the liver, both sesamin and episesamin significantly suppressed cholesterol accumulation. Interestingly, only episesamin significantly increased the activity of microsomal cholesterol 7alpha-hydroxylase. 4. These results indicate that sesamin may be effective in preventing cholesterol accumulation in the liver. In comparison with sesamin, episesamin may be effective in the regulation of cholesterol metabolism in the serum and liver.

食環境因子による血清リポタンパク質代謝の変動機構に関する研究

It is well known that dietary xenobiotics and protein nutrition affect cholesterol and serum lipoprotein metabolism, although these precise mechanism has not been fully clarified. Treatment of rats with xenobiotics such as polychlorinated biphenyls (PCB) resulted in hyper-α-lipoproteinemia, characterized by an increase of apolipoprotein A-I (apo A-I) and replacement of apo E by apo A-I. Dietary PCB increased the hepatic levels of mRNA for apo A-I and HMG-CoA reductase. In hepatocyte culture, a direct effect of PCB on hepatocytes was revealed. The dietary level of protein regulated the expression of the liver apo A-I gene transcriptionally in a liver-specific manner. Soy protein isolate (SPI) decreased the cholesterol level of very-low-density lipoproteins and of high-density lipoproteins in comparison with casein. SPI lowered the level of apo E-rich lipoproteins, and then decreased that of apo A-I-rich lipoproteins. The hepatic apo A-I mRNA level was decreased by SPI, and elevated by addition of methionine. These results demonstrate that dietary xenobiotics and protein are regulators of apo A-I gene expression and the serum level of high-density lipoproteins.

Treatment of cerebrotendinous xanthomatosis: effects of chenodeoxycholic acid, pravastatin, and combined use

Treatments by oral administration of chenodeoxycholic acid (CDCA) alone, 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitor (pravastatin) alone, and combination of the two drugs were attempted for 7 patients with cerebrotendinous xanthomatosis (CTX). CDCA treatment at a dose of 300 mg/day reduced serum cholestanol (67.3% reduction), lathosterol (50.8%), campesterol (61.7%) and sitosterol (12.7%). However, the sera of the patients changed to be “atherogenic”; total cholesterol, triglyceride and low-density lipoprotein (LDL)-cholesterol were increased, while high-density lipoprotein (HDL)-cholesterol was decreased. Contrarily, pravastatin at a dose of 10 mg/day improved the sera of the patients to be markedly “anti-atherogenic”, but the reductions of cholestanol (30.4%), lathosterol (44.0%), campesterol (22.9%) and sitosterol (9.6%) were inadequate. Combined treatment with CDCA and pravastatin showed good overlapping of the effects of each drug alone. The sera of the patients were apparently more “anti-atherogenic” than those after CDCA treatment. Serum cholestanol concentration was still 2.7 times higher than in controls, but the serum lathosterol level was within the normal range, indicating that the enhancement of overall cholesterol synthesis in the patients was sufficiently suppressed. Plant sterol levels were also within the normal range. The combination of CDCA and pravastatin was a good treatment for CTX, based on the improvement of serum lipoprotein metabolism, the suppression of cholesterol synthesis, and reductions of cholestanol and plant sterol levels. In all of 7 patients, the progression of disease was arrested, but dramatic effects on clinical manifestations, xanthoma, and electrophysiological findings could not be found after the treatment of these drugs.

Effects of sesamin on serum lipoprotein metabolism in normocholesterolemic and hypercholesterolemic stroke-prone SHR.

Effects of sesamin on serum lipoprotein metabolism in normocholesterolemic and hypercholesterolemic stroke-prone SHR.

Serum Lipoproteins During Treatment with Antihypertensive Drugs

Several drugs used for antihypertensive therapy may modify the lipoprotein metabolism. Thiazides in high dosage and loop diuretics can increase serum low-density lipoprotein (LDL) cholesterol and/or very-LDL cholesterol and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio, while HDL cholesterol is largely unchanged; triglycerides (Tg) are also often elevated. Premenopausal women may be protected from this side effect. Whether diuretic-induced dyslipidemia is dose-dependent and low thiazide doses (i.e., hydrochlorothiazide < or = 12.5 mg daily) are interacting less, awaits clarification. beta-Blockers without intrinsic sympathomimetic activity increase serum triglycerides and tend to lower the potentially antiatherogenic HDL cholesterol. The diuretic-antihypertensive agent indapamide, given at a dose of 2.5 mg/day, is neutral with regard to serum lipoprotein and glucose metabolism. The potassium-sparing diuretic spironolactone, conventional sympatholytic agents, calcium-channel blockers, and probably the serotonin2-receptor antagonist ketanserin, exert no relevant effects on the lipoprotein profile. Angiotensin-converting enzyme inhibitors may slightly decrease serum triglycerides. alpha 1-Receptor blockers slightly decrease LDL cholesterol and Tg and increase HDL cholesterol. Drug-induced development or aggravation of dyslipidemia represents a potentially adverse influence. In the hypertensive population, effective blood pressure control with traditional drug therapy based on thiazide-type diuretics in high dosage led to a distinct decrease in cerebrovascular morbidity and mortality, but failed to satisfactorily reduce coronary complications. The prognostic relevance of drug-induced changes in serum lipoproteins, carbohydrate metabolism and other risk factors or correlates awaits further clarification.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of diuretics on the plasma lipid profile.

Hypertension, dyslipidaemia, glucose intolerance (associated with insulin resistance and compensatory hyperinsulinaemia) and other abnormalities are complementary coronary risk factors which often occur in association. A familial trait for essential hypertension seems to coexist commonly with defects in carbohydrate and lipoprotein metabolism which can be detected before the appearance of hypertension. Diabetes mellitus as well as obesity promotes the development of hypertension and dyslipidaemia. Moreover, certain drugs used for antihypertensive therapy can further modify lipoprotein and glucose metabolism. Thiazides in high dosage and loop-diuretics can increase serum low-density-lipoprotein cholesterol (LDL-C) and/or very-LDL-C and the total C/high-density lipoprotein cholesterol (HDL-C) ratio, while HDL-C is largely unchanged; triglycerides (Tg) are also often elevated. Premenopausal women may be protected from this side effect. Whether diuretic-induced dyslipidaemia is dose-dependent and low thiazide doses (i.e. hydrochlorothiazide < or = 12.5 mg daily) are less active, awaits clarification. The diuretic-antihypertensive agent, indapamide, given at a dose of 2.5 mg.day-1, seems to exert no relevant effect on serum lipoprotein or glucose metabolism. The potassium-sparing diuretic, spironolactone, also may be largely neutral with regard to lipids. Moreover, potassium sparing diuretics may possibly counteract, at least in part, a dyslipidaemic influence of potassium-loosing diuretics in medium dose. Drug-induced dyslipidaemia, as well as glucose intolerance, represent potentially adverse influences. In the hypertensive population, effective blood pressure control with traditional drug therapy based on thiazide-type diuretics in high dosage led to a distinct decrease in cerebrovascular morbidity and mortality, but a lesser decrease in coronary events.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Magnesium Administration on Serum Lipoprotein Metabolism in SHRSP

Effect of Magnesium Administration on Serum Lipoprotein Metabolism in SHRSP

Alteration of Serum Lipoprotein Metabolism by Polychlorinated Biphenyls and Methionine in Rats Fed a Soybean Protein Diet

The effects of dietary supplementation of methionine to a 20% soybean protein isolate diet on serum lipoprotein profiles and secretion rate of VLDL in rats receiving polychlorinated biphenyls (PCB) were investigated. Serum cholesterol levels were higher in rats fed PCB or a methionine supplement than in controls. The effects of PCB and methionine were synergistic. The feeding of PCB resulted in more cholesterol in all fractions of serum lipoproteins tested, especially HDL (HDL1 and HDL2). Dietary supplementation of methionine primarily increased HDL cholesterol. The elevation of serum lipoprotein cholesterol due to PCB and/or methionine was significant in HDL1, which showed alpha-mobility. These results showed that methionine and PCB significantly influenced HDL metabolism. The secretion rate of VLDL was higher in rats fed PCB than in controls, but the addition of methionine to diets did not affect the secretion rate of VLDL cholesterol. This implies that PCB increased serum cholesterol partly through the stimulation of VLDL cholesterol secretion.

Reduction of serum lipoprotein(a) levels in hyperlipidaemic patients with α-tocopheryl nicotinate

The effect of low dose (600 mg/day) α-tocopheryl nicotinate on serum lipoprotein(a) (Lp(a)) concentration was studied in 28 hyperlipidaemic patients. Serum lipids, lipoproteins and apolipoproteins, except for Lp(a), tended to increase after treatment. In particular, the changes in HDL-cholesterol and apo C-II levels were statistically significant. On the other hand, serum Lp(a) levels in all patients decreased significantly after 2 months of treatment. Furthermore, no difference between before and after treatment was observed in the group with initial Lp(a) levels < 18 mg/dl, whereas Lp(a) concentrations decreased significantly after treatment in the group with levels ⩾ 18 mg/dl. The effects of probucol and α-tocopheryl nicotinate on serum Lp(a), total cholesterol and HDL-cholesterol were entirely different. Possible mechanisms of α-tocopheryl nicotinate on serum Lp(a) and lipoprotein metabolism are discussed.

Effects of short- and long-term administration of nifedipine on serum lipoprotein metabolism in patients with mild hypertension

The effects of short- and long-term administration of nifedipine on serum lipids, lipoproteins, and apolipoproteins (apo) were studied. Administration of nifedipine capsule for 4 months significantly decreased triglycerides and increased the HDL2 cholesterol and the HDL2/HDL3 cholesterol ratio. No significant changes in serum lipids and lipoproteins were observed during short-term therapy with slow-release nifedipine tablets. Following administration of tablets for 24 months, the LDL/HDL cholesterol ratio, apo B, and apo B/apo A-I ratio increased at 12 months, but reverted to baseline values at 24 months. Apo E levels were decreased significantly at 24 months. No significant changes were noted in total cholesterol, triglyceride, HDL cholesterol, HDL2,3 cholesterol, apo A-I, apo A-II, apo C-II, or apo C-III levels during long-term therapy with slow-release nifedipine tablets. These results indicate that nifedipine has a neutral or even favorable effect on lipoprotein metabolism. However, a prospective well-controlled study would be required to finally establish this effect. This finding strengthens the indications for using nifedipine as a first-line drug in the long-term treatment of hypertension.

Lipoproteins and Acute Phase Response during Acute Infection. Interrelationships between C-reactive Protein and Serum Amyloid-A Protein and Lipoproteins

To study the interrelations between the changes of acute phase proteins and those of serum lipoproteins in acute infections we measured the concentrations of different lipoproteins, serum amyloid-A protein and C-reactive protein and activities of lipoprotein lipase and hepatic lipase during acute and convalescence phase and after complete recovery in 64 patients with infectious diseases (30 with viral infection and 34 with bacterial infection). The maximal decrements of both low density lipoprotein and high density lipoprotein cholesterol correlated significantly with the acute phase levels of C-reactive protein and serum amyloid-A protein. The acute phase concentration of very low density lipoprotein triglyceride correlated inversely to C-reactive protein level (r = -0.31, P less than 0.05) but not to serum amyloid-A protein level. Regression analysis showed that the concentration of C-reactive protein was a significant predictor of very low density lipoprotein triglyceride level in the acute phase of infection but not during convalescence. These results and the previous findings that C-reactive protein binds to low and very low density lipoproteins and that serum amyloid-A protein is associated with high density lipoprotein give credence to the view that C-reactive protein and serum amyloid-A protein interfere with the metabolism of serum lipoproteins during acute phase of infection.

高コレステロール食飼育ウサギにおけるPantethine・Soysterol配合剤の高脂血症改善作用と動脈硬化抑制効果について

高コレステロール食飼育ウサギにおけるPantethine・Soysterol配合剤の高脂血症改善作用と動脈硬化抑制効果について

The effect of gossypol on serum lipoproteins of adult rats.

It has been shown that gossypol treatment brings about marked changes in plasma lipoproteins of certain species causing a marked fall in total cholesterol and LDL-cholesterol levels. Using Helena electrophoretic system the lipoprotein pattern in serum of adult rats treated with gossypol was studied. Gossypol treatment for 1 day and 7 days continuously did bring about changes in serum lipoprotein profile. A marked increase in VLDL-cholesterol and fall in LDL-cholesterol was observed in rats treated with gossypol which was more pronounced in the 7 days treated group. It did not bring about any marked change in total cholesterol level. It did cause an increase in serum triglyceride level. Heparin injection which brought about a fall in VLDL-cholesterol with a concomitant increase in HDL-cholesterol in control rats did not elicit changes in gossypol-treated rats. Thus, gossypol treatment appears to alter serum lipoprotein metabolism in rats also.

Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--effect of taurine on serum lipoprotein metabolism in hypercholesterolemic rats

It is well known that taurine, a final metabolite of sulfur-containing amino acids, plays an important role in bile acid metabolism and that it also has a moderately hypotensive effect. Moreover, it has recently been revealed that taurine shows a hypocholesterolemic effect in animals with experimentally induced hypercholesterolemia. However, the hypocholesterolemic mechanism remains unresolved. Stroke-prone spontaneously hypertensive rats (SHRSP) easily develop hypercholesterolemia when fed a high-fat and high-cholesterol diet (HFC diet). In our previous paper, we reported changes in the concentrations and distributions of serum lipoproteins and apolipoproteins in hypercholesterolemic SHRSP and Kyo: Wistar rats (WKY) induced by HFC feeding. In this paper, to elucidate the mechanism of the hypocholesterolemic effect of taurine, we investigated the effects of taurine on concentrations and distributions of serum lipoproteins and apolipoproteins in hypercholesterolemic SHRSP and WKY induced by HFC feeding. The results obtained were as follows: 1) The hypocholesterolemic effect of taurine in hypercholesterolemic SHRSP was remarkable in comparison with that in hypercholesterolemic WKY. 2) The hypocholesterolemic effect of taurine was mainly due to a marked suppression of extreme elevations of cholesterol contents in the VLDL and IDL fractions of both strains. This was associated with a decrease in the elevated contents of apo B and apo E which are major components of VLDL and IDL. This suppressive effect was more obvious in SHRSP than in WKY, which explains the greater hypocholesterolemic effect of taurine in SHRSP. It could be that, as a result of taurine administration, the catabolism of cholesterol to bile acid in the liver is accelerated, followed by a decrease of the hepatic cholesterol pool, resulting in a suppression of the synthesis and/or secretion of VLDL (beta-VLDL) in the liver. 3) The hypocholesterolemic effect of taurine was also observed in the LDL fractions of both strains, but the effect was not as strong as that observed in the VLDL and IDL fractions. This effect might be attributable to suppression of the synthesis and/or secretion of LDL in the liver and a decrease in the elevated content of apo E HDL (HDLc) which spans two density fractions (the LDL and HDL fractions). 4) In HDL fractions of both strains, the decreased content of apo E HDL (HDL1 and HDLc) was even lower, whereas the decreased apo A-I content in the HDL fraction of SHRSP was significantly restored and the cholesterol level was slightly elevated.(ABSTRACT TRUNCATED AT 400 WORDS)

Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet - Effects of salt intake on serum lipoprotein and apolipoprotein metabolism.

Recently, food intake in Japan has been characterized by an increase in fat intake, especially animal-fat intake and the maintenance of excess salt (sodium chloride) intake. It is generally accepted that the increase in fat intake is closely related to atherosclerosis, and excess salt intake is a high risk factor for the development of hypertension and cerebrovascular lesions. So far, in almost all reports, the increase in fat intake and excess salt intake have been studied independently, and there have been few reports on the combined effects of these two factors. Taking the above things into consideration, it would seem to be very interesting to investigate the effect of excess salt intake on lipid metabolism. In this paper, we studied the effects of excess salt intake on lipoprotein and apolipoprotein metabolisms, using stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Kyo: Wistar rats (WKY) as model animals. The results obtained were as follows: A significant increase in the concentration of serum total cholesterol (TC) was observed in SHRSP and WKY, when the rats were given a regular diet (CE-2, Clea Japan Inc.) and 1% sodium chloride solution (1% NaCl) as drinking water for 4 weeks. This was accompanied by a tendency toward increases in the concentrations of serum apolipoproteins in both strains. These results suggest that excess salt intake could accelerate the production of serum total lipoproteins in SHRSP and WKY, when the rats are fed a regular diet. Next, 1% NaCl and a high-fat and high-cholesterol diet (HFC diet) were simultaneously given to SHRSP and WKY for 6 weeks. The effects of simultaneous administration on lipoprotein and apolipoprotein metabolisms were compared with those of HFC feeding. One percent NaCl did not markedly affect hypercholesterolemia in WKY, while it induced more marked hypercholesterolemia in SHRSP that was associated with extreme elevations of serum TC and the atherogenic index (A.I.). This deleterious effect of 1% NaCl in SHRSP was due to drastic elevations of cholesterol contents in the very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) fractions. This was also associated with marked increases in apo B contents in the VLDL, IDL and LDL fractions and significant increases in apo E contents in the VLDL and IDL fractions. These results indicate that 1% NaCl induced much larger increases in serum atherogenic beta-lipoproteins in SHRSP.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of 2-(2,4-dimethylphenyl)indan-1,3-dione on serum lipoprotein and lipid metabolism of rodents.

2-(2,4-Dimethylphenyl)indan-1,3-dione was shown to be a potent hypolipidemic agent in rodents, lowering significantly both serum cholesterol and triglyceride levels at 20 mg/kg/day. The agent in vivo inhibited the enzymatic activities of ATP-dependent citrate lyase, acetyl-CoA synthetase, cholesterol-7-alpha-hydroxylase, acyl-CoA cholesterol acyl transferase, sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase. Tissue lipid levels of liver and small intestine also were reduced by the agent. The rat serum lipoprotein lipid content was modulated by the drug, which should be favorable for the removable of cholesterol from peripheral tissue for conduction to the liver for clearance from the body. Low density lipoprotein (LDL) cholesterol levels were reduced after treatment, which suggests that the agent potentially reduces deposition of cholesterol in plaques. If chemotherapy for atherosclerosis is to be successful, then the high density lipoprotein (HDL) cholesterol level needs to be elevated more than 16% to 25%, the level produced by current hypolipidemic agents. 2-(2,4-Dimethylphenyl)indan-1,3-dione offers a 75% increase in HDL cholesterol levels and a 30% reduction of LDL cholesterol levels with a suppression of de novo synthesis of lipids and a reduction of tissue cholesterol deposition.

Effect of dichlorvos on the activity of lipoprotein lipase from adipose tissue, on plasma lipids and postheparin lipolytic plasma activity in rats.

The activity of lipoprotein lipase (LPL) from adipose tissue, the postheparin lipolytic activity (PHLA) in plasma, and the content of plasma lipoproteins were investigated in rats poisoned with dichlorvos (DDVP). Administration of a single dose (50% LD50) resulted in inhibition of LPL and PHLA; the greatest inhibition was observed at 24 and 48 h after administration of the posticide. The metabolism of serum lipoproteins was also altered; the content of triacylglycerols in very low density lipoproteins (VLDL) and low density lipoproteins (LDL) fractions was increased; the content of cholesterol was increased in VLDL and high density lipoproteins (HDL) fractions, and decreased in the LDL fraction. On repeated administration of small DDVP doses (5% LD50) the greatest changes were observed after 90 days of intoxication. The levels of all three determined lipoprotein fractions, as well as PHLA, were decreased. The LPL activity in adipose tissue was slightly raised. The results suggest that DDVP interferes with the metabolism of lipids.

Effect of Probucol, Pantethine and Their Combinations on Serum Lipoprotein Metabolism and on the Incidence of Atheromatous Lesions in the Rabbit

AbstractEffect of probucol. pantethine and their combinations on serum lipoprotein metabolism and on the incidence of atheromatous lesions in aorta and coronary artery was studied in cholesterol-fed rabbits. Probucol ireatment (0.5% in diet) resulted in reducing HDL cholesterol and serum apo A-l levels significantly, while paniethine treatment (0.25%–0.75% in diet) tended to increase HDL cholesterol and serum apo A-l levels. Combined treatment with these two drugs showed a significant prevention in the reduction of HDL cholesterol and serum apo A-l levels by probucol alone. Probucol or pantethine treatment reduced effectively (V)LDL cholesterol and serum apo B levels, and these effects were accelerated additively when the two drugs were given concurrently. Atheromatous lesions in aorta and coronary artery in cholesterol-fed rabbits were prevented by the treatment with probucol (0.5% in diet) or pantethine (0.75% in diet) for 24 weeks. The combined treatment with these two drugs showed more marked prevention than either drug alone. From these findings, it is concluded that the combined treatment of probucol with pantethine is effective for improvement of serum lipoprotein disorders and for prevention of the incidence of atheromatous lesions in aorta and coronary artery in cholesterol-fed rabbits.