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PubMed1985

Effect of dietary cholesterol and cholestyramine on developmental pattern of 3-hydroxy-3-methylglutaryl-CoA reductase.

Supplementation of the diet with 2% cholesterol suppressed the increase observed in the hepatic and intestinal 3-hydroxy-3-methylglutaryl-CoA reductase activity from normally fed chicks during the first days after hatching. Cholestyramine feeding clearly increased both hepatic and intestinal reductase activities. In contrast, brain reductase did not show significant changes by cholesterol or cholestyramine feeding. Dietary cholesterol produced a clear increase in the cholesterol/lipidic phosphorus molar ratio of hepatic and intestinal microsomal membranes. However, this molar ratio did not change by cholestyramine feeding during postnatal development. Both dietary cholesterol and cholestyramine had practically no effect on the cholesterol/lipidic phosphorus molar ratio of brain microsomes. The relationship between the inhibition of reductase activity by dietary cholesterol and the increase of cholesterol/lipidic phosphorus molar ratio is in agreement with a mechanism of regulation of both hepatic and intestinal reductase by alterations of membrane fluidity, mechanism that would be already operative during the neonatal period.

Animals↗

PubMed1989

Induction of mRNA for low-density lipoprotein receptors in heterozygous Watanabe heritable hyperlipidemic rabbits treated with CS-514 (Pravastatin) and cholestyramine.

We administered CS-514, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, alone and in combination with cholestyramine to heterozygous Watanabe heritable hyperlipidemic rabbits. This rabbit model for heterozygous familial hypercholesterolemia has hepatic low-density lipoprotein receptors that are assumed to be half as many as in normal rabbits. CS-514 alone lowered plasma low-density lipoprotein cholesterol levels by 50%, and in combination with cholestyramine, it lowered levels by 80%. The membrane-binding assay showed these drugs caused 1.5- and 1.8-fold increases in the number of hepatic low-density lipoprotein receptors, respectively. We also measured the amount of mRNA for low-density lipoprotein receptor by S1 nuclease protection assay in the same livers as above. These drugs induced mutant mRNA for the low-density lipoprotein receptor, which has an in-flame deletion of 12 nucleotides, as well as normal receptor mRNA. CS-514 alone produced a 1.8-fold increase in the amount of mRNA for the normal receptor and a 2.3-fold increase for the mutant mRNA, whereas CS-514 in combination with cholestyramine produced 1.9- and 3.1-fold increases, respectively. We conclude that CS-514 induces mRNA for the low-density lipoprotein receptor, subsequently increasing the receptor protein in the liver, and then reduces the levels of plasma cholesterol, and that the induction is augmented when the drug is administered in combination with cholestyramine.

Animals↗

PubMedDate not supplied

Effects of cholestyramine and parenteral nutrition on hepatic metabolism of lidocaine: a study using isolated rat liver perfusion.

BACKGROUND: The effect of an oral bile salt binder, cholestyramine, on parenteral nutrition-related hepatic dysfunction and lidocaine metabolism was studied in rats. METHODS: Rats were randomly assigned to one of three treatment groups: the PN group received infusions of dextrose and amino acids; the PNC group was treated the same as the PN group, but also received oral cholestyramine; CF group animals were fed rat food and water. Lidocaine metabolism was studied in livers isolated from animals after 7 days of parenteral nutrition. RESULTS: No differences in liver function test values of PN and PNC groups were detected compared with group fed rat food. However, lidocaine metabolism was found to be significantly reduced in both the PN and PNC groups. Significant reductions were observed in the hepatic extraction ratio (23% and 15%) and in intrinsic clearance (61% and 53%) in PN and PNC animals, respectively (p < .05). Material balance at steady state showed that recovery of lidocaine was threefold higher in the PN group and twofold higher in the PNC group than the rat food group (p < .05). Metabolite-to-drug ratios were determined for each lidocaine metabolite and this revealed significant reductions in N-dealkylation (64% and 57%) and aryl methyl hydroxylation (92% and 86%) in PN and PNC animals, respectively (p < .05). CONCLUSIONS: Histologic findings suggest that cholestyramine feeding prevented liver dysfunction, possibly through interruption of secondary bile salt reabsorption. However, lidocaine metabolism was still impaired after cholestyramine ingestion; the impairment mechanism remains unknown.

Amino Acids↗

PubMedDate not supplied

Chronic diarrhoea in non collagenous microscopic colitis: therapeutic effect of cholestyramine.

Chronic watery diarrhoea is the main symptom of the microscopic colitis syndrome, including collagenous colitis (CC), lymphocytic colitis (LC), and not otherwise specified (NOS) colitis. The goal of this study was to evaluate the anti-diarrhoeal effect of cholestyramine in non collagenous microscopic colitis. The records of 13 patients with LC and 7 patients with NOS, who had received cholestyramine as first line therapy and who responded to a questionnaire, were reviewed. On an intention to treat basis, a good clinical effect of cholestyramine was achieved in 75 % of the patients in both LC and NOS colitis. There was no therapeutic effect in 15 % of the patients, who all had LC. In general, the anti-diarrhoeal effect appeared within one week of treatment. Cholestyramine provides a rapid and adequate symptomatic relief of the diarrhoea in non collagenous microscopic colitis.

Adult↗

PubMed1983

[Carcinogenicity study of cholestyramine in rats].

Carcinogenicity study on cholestyramine, an anti-hypercholesterolemic agent, was carried out using Fischer rats by feeding with a normal pellet diet (control) and with three sorts of the pellet diets in which cholestyramine was admixed in the common diet at the rates of 1.25, 2.5 and 5%, respectively. The animals were fed with these diets for 26 months and a normal diet for subsequent 2 months. Some of the male rats fed with the 5% admixed diet revealed a slight growth retardation and occasionally hemorrhagic tendency, without resulting in severe macroscopic and microscopic lesions of the internal organs and in shortening of the mean survival time as compared with that of the control group. The rates of tumor-bearing animals were high in all experimental groups including the control, but the rates were not considered to be drug-related. Incidences of individual tumors were not significantly different each other between cholestyramine-fed groups and control group. Thus, it was not recognized that cholestyramine induced any drug-related specific tumors and an accelerated growth of any tumors.

Animals↗

PubMed1992

Comparison between lovastatin and cholestyramine in the treatment of moderate to severe primary hypercholesterolaemia.

120 patients (64 men, 56 women) aged 19-66 years with primary hypercholesterolaemia (mean serum total cholesterol 10.1 mmol/l, range 6.5-16.3 mmol/l) with normal or moderately raised concentrations of serum triglycerides were randomised after four weeks' diet and four weeks' diet+placebo phase either to cholestyramine (40 patients) or lovastatin (80 patients) treatments for the succeeding 12 weeks. The maximal daily doses were 24 g of cholestyramine and 80 mg of lovastatin. The baseline data of the treatment groups were comparable with the exception of HDL-cholesterol concentrations, which were lower in the lovastatin group. The mean reductions in total serum cholesterol concentrations were 24.3% for cholestyramine (P less than or equal to 0.01) and 33.4% for lovastatin (P less than or equal to 0.01) (P less than or equal to 0.01 between the treatment groups), in LDL-cholesterol 32.1% (P less than or equal to 0.01) and 40.7% (P less than or equal to 0.01) (P less than or equal to 0.05 between the treatment groups) and in apolipoprotein B 23.3% (P less than or equal to 0.01) and 33.3% (P less than or equal to 0.01) (P less than or equal to 0.01 between the treatment groups), respectively. Lovastatin was the only drug to reduce serum triglyceride concentrations, it did so by 26.0%. HDL-cholesterol increased by 7.7% (P = NS) when cholestyramine was taken and by 13.5% (P less than or equal to 0.05) with lovastatin (P = NS between the treatment groups). Apolipoprotein A1 remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2003

The effect of taurine on the cholesterol metabolism in rats fed diets supplemented with cholestyramine or high amounts of bile acid.

The effects of taurine on serum cholesterol levels and hepatic cholesterol 7alpha-hydroxylase activity (CYP7A1) were studied in rats fed cholestyramine or high amounts of sodium cholate in order to alter the intestinal pool of bile acids. Rats were fed a diet supplemented with 1% cholesterol and 0.25% sodium cholate (high cholesterol, control; C), and C supplemented with 4% cholestyramine (CH) or 0.75% sodium cholate (BA) for 14 d. Taurine groups were fed the diet supplemented with 3% taurine (CT, CHT and BAT). Compared to rats fed C and BA diets, serum cholesterol levels were significantly reduced in rats fed CT and BAT diets, but a significant reduction of serum cholesterol by taurine feeding was not observed in the CHT group as compared to the CH group. An increase in hepatic CYP7A1 activity due to taurine intake was observed in the CT and BAT groups. However, the simultaneous administration of cholestyramine and taurine (CHT group) did not increase hepatic CYP7A1 activity compared the intake of cholestyramine only (CH group). A significant increase in fecal bile acid excretion due to taurine intake was found only in rats fed the CT diet. In conclusion, it is suggested that taurine facilitates hepatic CYP7A1 activity regardless of the enlarged intestinal pool of bile acids due to increased intake of exogenous bile acid, and then reduces the serum cholesterol concentration.

Animals↗

PubMed1996

Effect of cholestyramine on the formation of pigment gallstone in high carbohydrate diet-fed hamsters.

This study was designed to investigate the effect of cholestyramine on the formation of pigment gallstones in high carbohydrate diet-fed hamsters and whether that effect occurred because of cholecystokinin action. Forty seven hamsters were divided into three groups: group I(n = 16) was fed on normal rodent chow(43% carbohydrate), group II(n = 14) was fed on a high CHO diet(65% carbohydrate), group III(n = 17) was fed on a high CHO diet containing 4% cholestyramine. Gallstones developed in 0% of group I, 42.9% of group II and 5.9% of group III(P < 0.05, group II vs III). To evaluate the chronic status of cholecystokinin level, the wet weight of pancreas and the average area of pancreatic acinar in microscopic high power field were measured. There was no significant difference between group II and group III in pancreatic weight and average area of pancreatic acinar(P > 0.05). In gallbladder bile analysis, there was also no significant difference between group II and group III in cholesterol, phospholipid, total calcium, total bilirubin and bile acid levels. In conclusion, cholestyramine decreases the frequency of pigment gallstone formation in high CHO diet-fed hamsters, but it is not clear whether the mechanism of cholestyramine decreasing the gallstone formation is due to the action of cholecystokinin.

Animals↗

PubMed1999

Antilithiasic effect of beta-cyclodextrin in LPN hamster: comparison with cholestyramine.

Beta-Cyclodextrin (BCD), a cyclic oligosaccharide that binds cholesterol and bile acids in vitro, has been previously shown to be an effective plasma cholesterol lowering agent in hamsters and domestic pigs. This study examined the effects of BCD as compared with cholestyramine on cholesterol and bile acid metabolism in the LPN hamster model model for cholesterol gallstones. The incidence of cholesterol gallstones was 65% in LPN hamsters fed the lithogenic diet, but decreased linearly with increasing amounts of BCD in the diet to be nil at a dose of 10% BCD. In gallbladder bile, cholesterol, phospholipid and chenodeoxycholate concentrations, hydrophobic and lithogenic indices were all significantly decreased by 10% BCD. Increases in bile acid synthesis (+110%), sterol 27-hydroxylase activity (+106%), and biliary cholate secretion (+140%) were also observed, whereas the biliary secretion of chenodeoxycholate decreased (-43%). The fecal output of chenodeoxycholate and cholate (plus derivatives) was increased by +147 and +64%, respectively, suggesting that BCD reduced the chenodeoxycholate intestinal absorption preferentially. Dietary cholestyramine decreased biliary bile acid concentration and secretion, but dramatically increased the fecal excretion of chenodeoxycholate and cholate plus their derivatives (+328 and +1940%, respectively). In contrast to BCD, the resin increased the lithogenic index in bile, induced black gallstones in 34% of hamsters, and stimulated markedly the activities of HMG-CoA reductase (+670%), sterol 27-hydroxylase (+310%), and cholesterol 7alpha-hydroxylase (+390%). Thus, beta-cyclodextrin (BCD) prevented cholesterol gallstone formation by decreasing specifically the reabsorption of chenodeoxycholate, stimulating its biosynthesis and favoring its fecal elimination. BCD had a milder effect on lipid metabolism than cholestyramine and does not predispose animals to black gallstones as cholestyramine does in this animal model.

Animals↗

PubMedDate not supplied

DEAE-Dextran in the treatment of primary hypercholesterolemia and/or hypercholesterolemia combined with hypertriglyceridemia. A multicentric randomized study on the efficacy of DEAE-Dextran compared with Cholestyramine.

This study was carried out to verify the therapeutic homogeneity between DEAE-Dextran and Cholestyramine. Blood levels of total cholesterol, HDL, LDL and triglycerides were evaluated in 202 patients affected by dyslipidemia and treated with DEAD-D at 2.5 g/day or with Cholestyramine at 12 g/day for 30 days. At the end of treatment both drugs caused significant reduction of total cholesterol, LDL and triglycerides blood levels; DEAD-D was generally more effective than Cholestyramine, in particular on triglycerides values (30.6% and 13.7% of reduction respectively), and produced also a significant increase in HDL cholesterol, differently from Cholestyramine that was ineffective on this parameter.

Anticholesteremic Agents↗

PubMed1992

Effects of long-term cholestyramine administration on vitamin D and parathormone levels in middle-aged men with hypercholesterolemia.

The objective of this study was to evaluate possible adverse effects of long-term bile acid-binding resin (cholestyramine) treatment on vitamin D, parathyroid hormone, and calcium levels in middle-aged men. A double-blind randomized clinical trial was carried out over a period of 7 to 10 years at the University of Minnesota's Lipid Research Clinic as part of the Lipid Research Clinic's Coronary Primary Prevention Trial. Two hundred and sixty-eight men aged 42 to 68 years who had been previously randomized in the CPPT to cholestyramine or placebo and who had taken at least 75% of the prescribed study medication (6 packets or 24 gm/day) as determined by packet counts for the duration of the Coronary Primary Prevention Trial including the last 4 months of the trial were studied: one group (n = 124) received cholestyramine and the other group (n = 144) received a corresponding dose of placebo. Serum samples were obtained at the time of the final study visit in cholestyramine and placebo groups. (Results are reported as mean +/- SD in SI units). There were no differences in plasma levels of calcium (2.3 +/- 0.1 mmol/L vs 2.3 +/- 0.1 mmol/L), phosphorus (0.99 +/- 0.14 mmol/L vs 0.98 +/- 0.12 mmol/L), albumin (45 +/- 3 gm/L vs 46 +/- 0.6 gm/L), calcifediol (62.6 +/- 29.2 nmol/L vs 63.4 +/- 28.4), 25(OH)D2 (14 +/- 11 nmol/L vs 12 +/- 10 nmol/L) or calcitriol (99 +/- 190 pmol/L vs 91 +/- 56 pmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

PubMed1991

Regulation of cholesterol biosynthesis in sitosterolemia: effects of lovastatin, cholestyramine, and dietary sterol restriction.

We investigated the effects of lovastatin, cholestyramine, and dietary sterol restriction on cholesterol synthesis and low density lipoprotein receptor function in freshly isolated mononuclear leukocytes from two unrelated sitosterolemic families. Total plasma sterol concentrations were elevated in the two homozygous sitosterolemic subjects (343 and 301 vs. 185 mg/dl in controls) and contained increased amounts of plant sterols and 5 alpha-saturated stanols (20% and 8% vs. less than 1% in controls), but were not significantly different from controls in the two heterozygous subjects. The rates of conversion of acetate to cholesterol by mononuclear leukocytes were subnormal in all homozygous and heterozygous subjects and correlated with markedly reduced microsomal 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase activity. In the two homozygous subjects, cholestyramine treatment decreased plasma sterols 29% and 35%, and yet was associated with a paradoxical decline in mononuclear leukocyte HMG-CoA reductase activity. In contrast, plasma sterol concentrations decreased 14% and 5%, and mononuclear leukocyte HMG-CoA reductase activities increased 13% and 46% in three control and one heterozygous subjects treated with cholestyramine, respectively. Plasma sterol concentrations in the homozygous subjects unexpectedly failed to decline during treatment with lovastatin or a low sterol diet. In distinction, plasma sterol concentrations in three control and one heterozygous subjects dropped 28% and 31%, respectively, during treatment with lovastatin. Both cholestyramine and low dietary sterols stimulated low density lipoprotein receptor function. These results demonstrate a marked abnormality in cholesterol homeostasis in patients with homozygous sitosterolemia with xanthomatosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Effects of pravastatin and cholestyramine on products of the mevalonate pathway in familial hypercholesterolemia.

Patients with heterozygous familial hypercholesterolemia (n = 12) were treated either with pravastatin, a specific inhibitor of HMG-CoA reductase, or cholestyramine, followed by a period of combined treatment with both drugs. Initially, these patients had increased serum levels of low density lipoprotein (LDL) cholesterol (8.77 +/- 0.48 mmol/l; SEM), lathosterol (5.32 +/- 0.60 mg/l), and ubiquinone (0.76 +/- 0.09 mg/l), while the serum dolichol concentration was in the normal range. Cholestyramine treatment (n = 6) decreased the levels of LDL cholesterol (-32%) and increased lathosterol (+125%), but did not change dolichol or ubiquinone levels in a significant manner. Pravastatin treatment (n = 6) decreased LDL cholesterol (-27%), lathosterol (-46%), and ubiquinone (-29%). In this case, the amount of dolichol in serum also showed a small but statistically insignificant decrease (-16%) after 12 weeks of treatment. Combined treatment with cholestyramine and pravastatin (n = 6) resulted in changes that were similar to, but less pronounced than, those observed during pravastatin treatment alone. In no case was the ratio between ubiquinone and LDL cholesterol reduced. Possible effects on hepatic cholesterol, ubiquinone, and dolichol concentrations were studied in untreated (n = 2), cholestyramine-treated (n = 2), and pravastatin-treated (n = 4) gallstone patients and no consistent changes could be observed. The results indicate that treatment with pravastatin in familial hypercholesterolemia decreases serum ubiquinone levels in proportion to the reduction in LDL cholesterol.

Adult↗

PubMedDate not supplied

[The efficacy of cholestyramine as a hypocholesterolemic agent and its tolerance in a Mexican population].

The tolerance and efficacy of cholestyramine (12-16 gr/day) was evaluated in 19 patients with primary type-IIa hyperlipoproteinemia. All patients were on an isocaloric low-cholesterol diet that began at least one month before entry, and was continued during the eight weeks of the study. Cholestyramine significantly (p less than 0.001) lowered the plasma levels of cholesterol and of low density lipoprotein cholesterol from means of 288 +/- 46 mg/dl to 244 +/- 44 mg/dl and from 221 +/- 50 mg/dl to 171 +/- 46 mg/dl respectively. These were reductions of 15 and 22%. The magnitude of response to cholestyramine was unrelated to age, sex, cause of the hypercholesterolemia (familial or polygenic) or basal cholesterol levels. The drug was well tolerated. Only one patient was excluded because gastrointestinal discomfort. Because of its safety and efficacy, cholestyramine can be recommended as a first choice drug in the treatment of hypercholesterolemia.

Adult↗

PubMed1990

Regulation of hepatic cholesterol metabolism in humans: stimulatory effects of cholestyramine on HMG-CoA reductase activity and low density lipoprotein receptor expression in gallstone patients.

To characterize the metabolic regulatory response to interruption of the enterohepatic circulation of bile acids, we examined the effects of cholestyramine treatment on the rate-limiting steps in cholesterol biosynthesis (HMG-CoA reductase) and bile acid production (cholesterol 7 alpha-hydroxylase) as well as on the heparin-sensitive binding of low density lipoproteins (LDL) (reflecting LDL receptor expression) in human liver. Altogether, 18 normolipidemic patients with uncomplicated cholesterol gallstone disease were treated with cholestyramine (8 g b.i.d.) for 2-3 weeks prior to cholecystectomy, and another 34 cholesterol gallstone patients served as untreated controls. Cholestyramine treatment stimulated cholesterol 7 alpha-hydroxylase more than sixfold, and increased both HMG-CoA reductase activity (552 +/- 60 pmol/min per mg protein vs 103 +/- 9 pmol/min per mg protein) and LDL receptor expression (6.1 +/- 0.8 ng/mg protein; n = 6 vs 2.2 +/- 0.3 ng/mg protein; n = 7). Moreover, there was a good correlation between HMG-CoA reductase activity and LDL receptor binding (rs = +0.71; n = 13), suggesting a simultaneous stimulatory effect to compensate for the increased hepatic cholesterol catabolism due to bile acid depletion caused by cholestyramine. Further evidence for this assumption was the finding of a significant relationship between cholesterol 7 alpha-hydroxylase activity and both LDL receptor expression (rs = +0.77; n = 13) and HMG-CoA reductase activity (rs = +0.76; n = 46). We conclude that in human liver a parallel stimulation of cholesterol synthesis and LDL receptor expression occurs in response to stimulation of bile acid synthesis.

Adult↗

PubMed1990

Regulation of cholesterol 7 alpha-hydroxylase in the liver. Purification of cholesterol 7 alpha-hydroxylase and the immunochemical evidence for the induction of cholesterol 7 alpha-hydroxylase by cholestyramine and circadian rhythm.

Two cholesterol 7 alpha-hydroxylase isozymes were purified from liver microsomes of cholestyramine-treated female rats by using anion exchange high performance liquid chromatography. These two cytochrome P-450 isozymes were similar in electrophoretic mobility, immunocross-reactivity, and Vmax but differed in Km for cholesterol, turnover number, and charges. Antibody against the major isozyme was raised in rabbit. This antibody specifically inhibited microsomal cholesterol 7 alpha-hydroxylase activity. Immunoblot of microsomal polypeptides indicated that microsomal cholesterol 7 alpha-hydroxylase enzyme levels were increased in parallel with cholesterol 7 alpha-hydroxylase activity upon the treatment of rats with diet supplemented with cholestyramine. Both cholesterol 7 alpha-hydroxylase activity and enzyme levels were drastically reduced immediately after the removal of cholestyramine from the diet. Cholesterol 7 alpha-hydroxylase activity was also detected in the microsomes of kidney, heart, and lung in about 7-27% of the level found in the liver. 3-Methylcholanthrene treatment induced cholesterol 7 alpha-hydroxylase activity and enzyme level. In contrast, pregnenolone-16 alpha-carbonitrile or dexamethasone treatment greatly depressed enzyme and activity in rats. Cholesterol 7 alpha-hydroxylase enzyme level was 2-3-fold higher in liver microsomes of rats maintained under the reversed light cycle than under the normal light cycle. In genetically obese Zucker rats, cholesterol 7 alpha-hydroxylase activity and enzyme level did not respond to the change in the light cycle, however, were induced to the same levels as in the lean rats by cholestyramine treatment. This study provided the first direct evidence that the bile acid feedback regulation and circadian rhythm of microsomal cholesterol 7 alpha-hydroxylase activity involved the induction of cholesterol 7 alpha-hydroxylase enzyme level.

Animals↗

PubMed1990

Comparison of simvastatin and cholestyramine in the treatment of primary hypercholesterolaemia.

The effects of simvastatin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on plasma lipid levels were compared with those of the bile acid sequestrant cholestyramine in a randomized parallel study of 60 subjects with primary hypercholesterolaemia. After a 12-week direct comparison period 37 subjects with inadequate cholesterol reduction received a combination of both drugs and all subjects were followed for a further 40 weeks. Simvastatin was more effective than cholestyramine in lowering total and LDL cholesterol levels and the LDL/HDL ratio (-31.7% v. -19.7% [P less than 0.01], -41.0% v. -31.8% [P less than 0.05] and -46.7% v. -33.6% [P less than 0.01], respectively at Week 12). Only simvastatin significantly increased the HDL cholesterol concentration (+13.3% [P less than 0.01] v. +6.4%). Cholestyramine increased plasma triglyceride levels by 37.5% (P less than 0.01) whereas simvastatin caused a slight non-significant reduction. Combined therapy produced a further decrease in total and LDL cholesterol levels, and in the LDL/HDL ratio, which was sustained for the duration of the study. Simvastatin was better tolerated than cholestyramine (P less than 0.01), and combining the two drugs enhanced efficacy without increasing the frequency of side effects.

Adult↗

PubMed1990

Hepatic low density lipoprotein receptors, HMG-CoA reductase, and plasma lipids and apolipoproteins in high- and low-responding rhesus monkeys: effect of cholestyramine treatment.

Plasma lipids and apolipoproteins, and hepatic LDL receptor and HMG-CoA reductase activities in biopsy samples were measured in high- and low-responding rhesus monkeys maintained on a cholesterol-rich and regular diets. The effect of a 30-day cholestyramine treatment on the above parameters under both dietary conditions was also determined. On the cholesterol-rich diet the high-responders, when compared to the low-responders, had several-fold increased plasma cholesterol and apoB concentrations and significantly lower HDL apoA-I and cholesterol concentrations. Hepatic LDL receptor and HMG-CoA reductase activities were not detectable in the high-responders, while the low-responders expressed a reduced number of LDL receptors of normal affinity. Administration of cholestyramine resulted in a rapid induction of the hepatic LDL receptors in the high-responders and a small additional increase in the low-responders. Cholestyramine treatment also stimulated the expression of the hepatic HMG-CoA reductase in both groups of monkeys. These changes were accompanied by a dramatic drop in plasma cholesterol and apoB concentrations in the high-responders and, to a lesser extent, in the low-responders. Plasma HDL concentrations in the high-responders rose to levels higher than those seen in the low-responders. The affinity and receptor number were similar in both groups of monkeys on the control diet, but the low-responders had significantly higher HMG-CoA reductase activities. Administration of cholestyramine during the control diet had a small but significant additional effect on the hepatic LDL receptors of the low-responders but not of the high-responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗