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PubMed1983

Effect of cholestyramine administration during pregnancy in the rat.

The effect of administration of cholestyramine on plasma cholesterol level and hepatic cholesterol and bile acid synthesis was investigated in pregnant and nonpregnant rats. Rates of cholesterol and bile acid synthesis were reduced by pregnancy in both control and cholestyramine-treated rats. Administration of cholestyramine throughout gestation and pregnancy failed either to lower plasma cholesterol level or to increase bile acid synthesis, while cholesterol synthesis was only moderately stimulated. It is suggested that pregnancy-induced alterations in hepatic bile flow and composition in the direction of cholestasis may be responsible for the decreased efficacy of cholestyramine given to the pregnant animal.

Animals↗

PubMed1993

The effect of the HMG-CoA reductase inhibitor simvastatin and of cholestyramine on hepatic apolipoprotein mRNA levels in the rat.

We have administered the hypolipaemic drugs simvastatin and cholestyramine to rats, both separately and together, to determine whether drug-induced changes in plasma apo lipoprotein levels occur through regulation of hepatic genes coding for apolipoproteins (apos) AI, AIV, E and B. Cholestyramine alone had little effect on either the plasma levels of the apolipoproteins studied or their hepatic mRNA levels. However, simvastatin, either alone or in combination with cholestyramine, produced marked changes in both of these parameters. While simvastatin plus cholestyramine lowered mRNAs for apo AIV, apo E and apo B by 50%, 37%, and 55%, respectively, the treatment resulted in an increase of 150% in apo AI mRNA. This combined drug treatment caused a lowering in plasma concentration of all four apolipoproteins which failed to reach significance with apo E. Relative to controls, the values decreased to 83 +/- 14% for apo AI, 67 +/- 8% for apo AIV and 73 +/- 15 for apo B. An important novel finding of the present study, was that hypolipaemic drugs caused the apo B mRNA levels in rat liver to decrease. Previous reports have shown that although dietary fat or hormones caused marked changes in the concentration of circulating lipoproteins, they failed to alter apo B mRNA content. We suggest that the synthesis of apo B is subject to both pre- and post-translational regulation.

Animals↗

PubMed1987

Cholestyramine treatment in early life. Immediate and delayed effects on arterial cholesteryl ester metabolizing enzymes in the rabbit.

Feeding of cholestyramine-enriched diet to weaned normocholesterolemic rabbits resulted in: lowering of plasma cholesterol and distinctly decreased activity of aortic acyl-CoA cholesterol acyl transferase with no changes in aortic acid and neutral cholesteryl esterase activity. At 9 weeks after cessation of cholestyramine treatment enhanced activity of both aortic esterases were noted despite normalization of plasma cholesterol. No evidence for the presence of plasma factor influencing esterases activity was found in lipoprotein-free serum from cholestyramine-treated animals. These studies show that cholestyramine treatment in early life causes immediate and delayed changes in rabbit arterial cholesteryl ester metabolizing enzymes.

Animals↗

PubMed1988

Effects of lovastatin alone and in combination with cholestyramine on serum lipids and apolipoproteins in heterozygotes for familial hypercholesterolemia.

We have studied the effect of lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase), alone and in combination with the bile acid sequestrant cholestyramine on lipid parameters in 30 heterozygous patients with familial hypercholesterolemia (FH) during a 20-week open trial. Lovastatin 40 mg bid (twice daily) decreased significantly total serum cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides and apolipoprotein B by 36%, 45%, 29% and 11%, respectively, while high density lipoprotein (HDL)-cholesterol and apolipoprotein A-I were increased significantly by 16% and 37%, respectively. These data are consistent with a reduction in both the number of LDL particles and in their cholesterol content. Addition of cholestyramine 4 g bid caused a significant further decrease in total serum cholesterol and LDL-cholesterol to a total of 43% and 61%, respectively. The addition of 4 g bid or 8 g bid of cholestyramine caused only minor changes in the other lipid parameters. No effect was found by these drugs on Lp(a) lipoprotein level. We conclude that lovastatin alone or in combination with a small dose of cholestyramine normalizes the lipid profile in most FH heterozygotes.

Adult↗

PubMed1991

Cholesterol lowering and bile acid excretion in the hamster with cholestyramine treatment.

Cholestyramine was administered to hamsters at 6 doses in the diet for 1 week. Plasma cholesterol, LDL + VLDL cholesterol and HDL cholesterol were measured after this period. Bile acid excretion was measured in faeces collected over the final 24 h of the experiment. A dose-response curve for each parameter measured was constructed using data from individual hamsters. For the bile acid and the cholesterol measurements a maximum response was observed at the highest doses. A correlation between the bile acids excreted over 24 h and the LDL + VLDL cholesterol showed that the maximum effect of cholestyramine on lowering plasma and lipoprotein cholesterol occurred at a submaximal excretion level of bile acids. Comparison of the efficiency of cholestyramine in reducing plasma cholesterol in the hamster with limited data in the dog and in man suggest that a greater lowering of plasma cholesterol is achieved in the dog and in man for an equivalent increase in bile acid excretion caused by the sequestrant. As is already known, cholestyramine treatment caused an increase in hepatic cholesterol 7 alpha-hydroxylase and HMG-CoA reductase activity. Interestingly in this study the novel observation was made that the bile acid sequestrant reduced the activity of hepatic acyl-CoA: cholesterol acyltransferase.

Animals↗

PubMed1991

Doxazosin and cholestyramine similarly decrease fatty streak formation in the aortic arch of hyperlipidemic hamsters.

The effect of doxazosin, an alpha-1 adrenergic inhibitor, on atherosclerosis was determined in hyperlipidemic hamsters. Control hamsters fed chow plus 0.05% cholesterol and 10% coconut oil were compared to chow baseline animals, and to those receiving either 10 mg/kg/day doxazosin, or 245 mg/kg/day cholestyramine in the atherogenic diet. During 8 weeks of treatment, plasma lipids, mean arterial pressure (MAP) and heart rate (HR) were measured, then the ascending aortic arch was examined en face. Numbers of subendothelial macrophage-foam cells/mm2 and their average size (microns 2) were determined, and Oil red O staining (micrograms ORO/mm2) was quantitated to estimate lipid accumulation. Ultracentrifugation of control plasma demonstrate that low density lipoprotein (LDL) carried most of the cholesterol, and very low density lipoprotein (VLDL) was rich in triglycerides. Compared to controls, doxazosin and cholestyramine similarly decreased plasma total and LDL plus VLDL cholesterols, and total triglycerides on average by 46%, 61% and 45% respectively. High density lipoprotein cholesterol was unchanged. Doxazosin also reduced MAP by 18% without affecting HR. In all hamsters, foam cells and lipid accumulated in a lesion-prone area characterized by elevated endothelial cell density, and a thick intima of basement membrane-like material layered over "pads" of smooth muscle cells. Compared to controls, doxazosin and cholestyramine uniformly reduced the number of foam cells/mm2, foam cell size and ORO staining on average by 66%, 29% and 56%, respectively. We conclude that doxazosin decreases plasma lipids and inhibits the development of the fatty streak to a similar level as cholestyramine treatment.

Adrenergic alpha-Antagonists↗

PubMed1991

Hypolipidemic effect and mechanism of ketoconazole without and with cholestyramine in familial hypercholesterolemia.

The hypocholesterolemic and metabolic effects of ketoconazole (400 mg/d) alone (inhibits cholesterol synthesis at 14 alpha-demethylation of lanosterol) and in combination with cholestyramine (12 g/d), were studied in nine women with xanthomatous familial hypercholesterolemia (FH). In addition to serum lipoprotein levels, cholesterol precursors, fecal steroids, and cholesterol absorption were measured before and during the drug treatments. Serum total and low-density lipoprotein (LDL)-cholesterol were reduced by 19% and 22% with ketoconazole; the respective changes were 16% and 21% for cholestyramine, and 31% and 41% for the combined ketoconazole and cholestyramine treatment. Serum triglycerides, very-low-density lipoprotein (VLDL)-and high-density lipoprotein (HDL)-cholesterol levels were unchanged. Accumulation of cholesterol precursors in serum suggested that ketoconazole inhibited cholesterol synthesis at delta 8-sterol levels. Serum and fecal lanosterols were increased up to 20-fold and were interrelated. Their maximal serum level was 1.3 mg/DL and the lanosterol contents were negatively related to the serum cholesterol levels. The intestinal absorption and total intestinal fluxes of cholesterol were reduced by 27% and 29%. Cholesterol and bile acid synthesis were decreased by ketoconazole only when combined with cholestyramine. The synthesis of chenodeoxycholic acid was deeply hindered by ketoconazole. Thus, ketoconazole efficiently lowers serum total and LDL-cholesterol levels in FH patients, probably by inhibiting cholesterol synthesis and absorption. Effective biliary and fecal outputs of cholesterol precursors prevent their excessive increase in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Fecal bile acid excretion and liver cholesterol synthesis after sucralfate and cholestyramine administration in the rat.

The relative ability of the resin cholestyramine and sucralfate (disucrose octasulfate) to bind bile acids in the gastro intestinal tract and increase fecal bile acid excretion has been studied in normal rats under standard diet. Plasma and liver cholesterol concentrations and in vitro cholesterol synthesis from 14C-acetate by liver slices, have been determined before and after one and three weeks of drug administration (0.5 or 1.0 g/100 g food). Plasma and liver cholesterol levels were unchanged after one week of treatment, but a moderate decrease in liver cholesterol content was observed after 3 weeks administration of cholestyramine and, to a lesser extent of sucralfate. Both drugs increase fecal bile acid excretion with a definitely higher effect of cholestyramine at either dose or period of administration. However, the resin produced a higher bile acid excretion after one week than after three weeks, whereas sucralfate effect increases with the time of administration. In vitro cholesterogenesis was clearly increased by cholestyramine and moderately by sucralfate although 14C-acetate incorporation into cholesterol was not quantitatively correlated to the amount of bile acid excreted in feces. The potential interest of sucralfate as bile acid sequestrant and hypocholesterolemic agent in man deserves further investigations.

Aluminum↗

PubMed2004

Efficacy and safety of rosuvastatin alone and in combination with cholestyramine in patients with severe hypercholesterolemia: a randomized, open-label, multicenter trial.

BACKGROUND: Patients with severe hypercholesterolemia may need greater cholesterol reductions than can be achieved with statin therapy alone. OBJECTIVE: The primary objective of this trial was to compare the efficacy of a combination of rosuvastatin plus cholestyramine with that of rosuvastatin alone for reducing low-density lipoprotein cholesterol (LDL-C) levels after 6 weeks of treatment. METHODS: In this open-label, multicenter, randomized, parallel-group, comparator trial, adult patients with severe hypercholesterolemia (LDL-C level, 190-400 mg/dL) received rosuvastatin 40 mg/d for 6 weeks after a 6-week dietary lead-in period and were then randomized to 6 weeks of treatment with rosuvastatin 80 mg/d alone or rosuvastatin 80 mg/d plus cholestyramine 16 g/d (8 g BID with meals). RESULTS: Of 153 eligible patients, 147 (83 men, 64 women; mean [SD] age, 54.5 [13.7] years; mean [SD] bodyweight, 81.3 [14.4] kg) received randomized treatment, and 144 had post baseline measurements and were included in the analysis. The mean (SD) reduction in LDL-C was 522% (13.0%) after treatment with rosuvastatin 40 mg, and the least squares mean (SE) reductions in LDL-C were 56.4% (1.8%) and 60.5% (1.8%) after treatment with rosuvastatin 80 mg alone (n = 69) and rosuvastatin 80 mg plus cholestyramine (n = 75), respectively. No significant differences between treatments were found for these or other lipid measurements. Incremental LDL-C reductions >30% were obtained in 29% (22/75) of patients receiving combination therapy and 4% (3/69) of patients receiving rosuvastatin alone. The combination therapy was less well tolerated, primarily due to gastrointestinal symptoms; otherwise, the treatments were generally well tolerated. CONCLUSION: In this group of patients with severe hypercholesterolemia, the combination of rosuvastatin 80 mg with cholestyramine 16 g/d did not provide a significantly greater efficacy benefit than rosuvastatin alone.

Aged↗

PubMed1997

Healthcare decisions and product labeling: results of a consumer comprehension study of prototype labeling for proposed over-the-counter cholestyramine.

This study was designed to determine whether randomly selected subjects could comprehend prototype consumer-oriented package labeling and inserts for over-the-counter cholestyramine, a nonsystemic lipid-lowering agent. The primary messages communicated in the label were that consumers should see their doctor before taking cholestyramine and should read the full package insert. In addition, the label communicated indication, dosage, and preparation, as well as key warnings about use with other medications. The insert reinforced the message about seeing the doctor before taking cholestyramine and before taking concurrent medications, further explained the purpose of the drug and its correct use, and provided information about the two types of cholesterol, risk factors for heart disease, and the importance of diet and exercise. A total of 1,806 randomly selected subjects were interviewed in their homes in 40 geographic regions. After examining the product container with one of the three labels being tested, they were given a questionnaire to test their understanding of the label communication points. They were then asked to read the package insert and tested on their understanding of the messages it communicated. Responses were analyzed by gender, age, and education level, as well as by label format. For the education-level subgroup analysis, the high-school-nongraduate group was supplemented by 419 subjects, for a total of 2,225 subjects. Statistical analyses were performed on completed questionnaires by an independent data analysis company. The net correct response to the two primary communication objectives was 99% among the total population. Responses to questions addressing the use of concurrent medications; types of cholesterol; purpose, dosage, and preparation of the medication; and diet and exercise were also clearly understood. This study showed a high level of comprehension of the purpose and correct use of cholestyramine among both high-school graduates and nongraduates.

Adolescent↗

PubMed1998

Effects of atorvastatin monotherapy and simvastatin plus cholestyramine on arterial endothelial function in patients with severe primary hypercholesterolaemia.

Endothelial dysfunction is an important early event in atherogenesis. Changes in arterial endothelial physiology were studied in patients with severe primary hypercholesterolaemia participating in an ongoing clinical trial evaluating atorvastatin and simvastatin. Endothelial function was assessed non-invasively using brachial ultrasound and the primary outcome measure was flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperaemia. Patients were studied upon entry while still using simvastatin 40 mg daily and again after a 10-week washout (baseline). Over the next 30 weeks, 20 patients received atorvastatin titrated up to 80 mg daily and 12 patients received simvastatin titrated up to 40 mg daily (plus cholestyramine 4 g daily in 10/12), followed by a final ultrasound study. During simvastatin washout, total and low density lipoprotein (LDL) cholesterol rose by a median 23-29% and 30-34%, respectively. During atorvastatin therapy, total and LDL cholesterol fell by a median of 41 and 46%, respectively, triglycerides fell by 45%, and high density lipoprotein (HDL) cholesterol rose by 10%. During simvastatin plus cholestyramine therapy, the respective median changes were - 32, - 39, - 44 and + 11%. Patients at baseline showed evidence of impaired FMD and this improved significantly on either treatment, from a median + 2.2 to + 5.5% on atorvastatin and from + 1.8 to + 4.5% on simvastatin plus cholestyramine (P < 0.01 for both treatments). Typical response in healthy subjects would be from + 8 to + 9%. FMD at baseline was correlated with HDL cholesterol (r=0.49, P < 0.01). Change in FMD was inversely correlated with baseline FMD (r=-0.54, P < 0.001). Endothelial dysfunction in primary hypercholesterolaemia was improved by treatment with atorvastatin or simvastatin plus cholestyramine and this effect may result in the prevention of future coronary events.

Adult↗

PubMed1980

Long-term follow-up of children with familial hypercholesterolaemia treated with cholestyramine.

35 children with the heterozygous form of familial hypercholesterolaemia (FH) who were followed for up to 8 years after starting on cholestyramine treatment showed a progressive decrease in compliance with therapy with time, so that only 55% remained on treatment after 6 years and only 48% after 8 years. Long-term compliance was significantly better in those starting treatment before age 10. Plasma-cholesterol was lowered in all children taking cholestyramine: for the group the mean reduction in plasma-cholesterol ranged from 26 to 44% during the years of the study, on a mean cholestyramine dose of around 0.4 g/kg/day. Cholestyramine thus effectively lowers plasma-cholesterol in FH, but for long-term use compliance is a problem in many children.

Adolescent↗

PubMed2000

Contractile responses in spontaneously diabetic mice. II. Effect of cholestyramine on enhanced contractile response of aorta to norepinephrine in C57BL/KsJ (db/db) mice.

To examine the possible role of low-density lipoprotein (LDL) cholesterol in the enhanced norepinephrine (NE)-induced contractile response seen in spontaneously diabetic mice (db/db mice), we examined the effect of chronic administration of cholestyramine on the NE-induced contraction. Although chronic cholestyramine (300 mg/kg, po for 1 month) significantly lowered total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and triglyceride, the plasma glucose and insulin levels were unaffected. The enhanced NE response in diabetic mice was not affected by the chronic administration of cholestyramine. The K(+)-induced contractile response was not different among nondiabetic, diabetic, and diabetic mice chronically treated with cholestyramine. These results suggest that neither LDL cholesterol nor triglyceride is involved in the enhancement of the NE-induced contractile response seen in spontaneously diabetic mice.

Animals↗

PubMed2001

In vitro and in vivo studies to assess the effectiveness of cholestyramine as a binding agent for fumonisins.

Several adsorbent materials were tested at I mg/ml for their in vitro capacity to adsorb fumonisin B1(FB1) from aqueous solutions. Cholestyramine showed the best adsorption capacity (85% from a solution containing 200 microg/ml FB1) followed by activated carbon (62% FB1). Bentonite adsorbed only 12% of the toxin from a solution containing 13 microg/ml FB1, while celite was not effective even at the lowest tested FB1 concentration (3.2 microg/ml). Cholestyramine was tested in vivo to evaluate its capacity to reduce the bioavailability of fumonisins (FBs) in rats fed diet contaminated with toxigenic Fusarium verticillioides culture material. Rats were exposed for one week to FBs-free diet, FBs-contaminated diet containing 6 or 20 microg/g FB1 + FB2 and the same FBs-contaminated diet added of 20 mg/g cholestyramine. The increase of sphinganine/sphingosine (SA/SO) ratio in urine and kidney of treated rats was used as specific and sensitive biomarker of fumonisin exposure. The addition of cholestyramine to the FBs-contaminated diets consistently reduced the effect of FBs by reducing significantly (P < 0.05) both urinary and renal SA/SO ratios.

Animals↗

PubMed1997

The influence of age on low density lipoprotein metabolism: effects of cholestyramine treatment in young and old healthy male subjects.

OBJECTIVE: The plasma concentration of low density lipoproteins (LDL) increases with age, mainly as the result of a reduced clearance of LDL. Because the conversion of cholesterol to bile acids is reduced with age, we hypothesized that the response of plasma LDL to stimulation of bile acid production would be different in young and old subjects. DESIGN, SUBJECTS AND SETTING: Comparison of the response to cholestyramine treatment in two groups of normolipidaemic, normal weight males: seven young (23-34 years) and eight old (64-73 years). Outpatients at the metabolic ward of a university hospital given a standardized diet of natural type. INTERVENTION: Cholestyramine was given 8 g b.i.d. for 3 weeks and continued during the second LDL turnover study. MAIN OUTCOME MEASURES: Kinetics of autologous radiolabelled LDL before and during treatment. Mean values of lipoprotein lipid levels obtained during the two turnover studies. Changes in LDL particle composition and LDL receptor affinity between the two study periods. RESULTS: Both age groups responded with decreased levels of LDL cholesterol and apolipoprotein-B (apoB), the change being more pronounced in the old subjects. The LDL apoB fractional catabolic rate was increased by approximately 11% in both groups. In contrast, there was a reduced ability in the old subjects to sustain their production rates for LDL apoB with resin therapy, resulting in a 23% reduction in LDL input. No effect on the apparent LDL apoB synthesis rate was observed in the young subjects. LDL particles isolated from cholestyramine-treated subjects were triglyceride-enriched and cholesterol-depleted, and showed a lowered affinity for the LDL receptor in tissue culture studies. CONCLUSIONS: The results demonstrate that stimulation of bile acid production by cholestyramine treatment decreases LDL cholesterol levels in both young and old subjects. This therapy increases LDL apoB elimination in both age groups, but reduction of apparent LDL apoB production is only seen in old subjects.

Adult↗

PubMed1983

Reduction of serum cholesterol in heterozygous patients with familial hypercholesterolemia. Additive effects of compactin and cholestyramine.

We studied the effects of the bile acid sequestrant cholestyramine, alone and in combination with the experimental agent compactin (ML-236B), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum levels of lipoproteins in 10 heterozygous patients with familial hypercholesterolemia. After cholestyramine treatment alone for 2 to 16 months, serum total and low-density lipoprotein cholesterol decreased by 20 and 28 per cent, respectively. With the addition of compactin for 12 weeks there was a 39 per cent total decrease in serum cholesterol from the control value--from 356 +/- 14 to 217 +/- 10 mg per deciliter (9.27 +/- 0.36 to 5.64 +/- 0.26 mmol per liter [mean +/- S.E.M.]; P less than 0.001)--and a 53 per cent decrease in low-density lipoprotein cholesterol--from 263 +/- 13 to 125 +/- 10 mg per deciliter (6.84 +/- 0.34 to 3.25 +/- 0.26 mmol per liter; P less than 0.001). High-density lipoprotein cholesterol, which had increased during cholestyramine treatment, remained at its higher level. No adverse effects were observed. If long-term safety can be demonstrated, the compactin-cholestyramine regimen may prove useful in heterozygous familial hypercholesterolemia. prove useful in heterozygous familial hypercholesterolemia.

Adult↗

PubMedDate not supplied

A new approach in gastroretentive drug delivery system using cholestyramine.

We prepared cellulose acetate butyrate (CAB)-coated cholestyramine microcapsules as a intragastric floating drug delivery system endowed with floating ability due to the carbon dioxide generation when exposed to the gastric fluid. The microcapsules also have a mucoadhesive property. Ion-exchange resin particles can be loaded with bicarbonate followed by acetohydroxamic acid (AHA) and coated with CAB by emulsion solvent evaporation method. The drug concentration was monitored to maintain the floating property and minimum effective concentration. The effect of CAB: drug-resin ratio (2:1, 4:1, 6:1 w/w) on the particle size, floating time, and drug release was determined. Cholestyramine microcapsules were characterized for shape, surface characteristics, and size distribution; cholestyramine/acetohydroxamic acid interactions inside microcapsules were investigated by X-ray diffractometry. The buoyancy time of CAB-coated formulations was better than that of uncoated resin particles. Also, a longer floating time was observed with a higher polymer:drug resin complex ratio (6:1). With increasing coating thickness the particle size was increased but drug release rate was decreased. The drug release rate was higher in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF). The in vivo mucoadhesion studies were performed with rhodamine-isothiocyanate (RITC) by fluorescent probe method. The amount of CAB-coated cholestyramine microcapsules that remained in the stomach was slightly lower than that of uncoated resin particles. Cholestyramine microcapsules were distributed throughout the stomach and exhibited prolonged gastric residence via mucoadhesion. These results suggest that CAB-coated microcapsules could be a floating as well as a mucoadhesive drug delivery system. Thus, it has promise in the treatment of Helicobacter pylori.

Adhesives↗

PubMed1986

3-Hydroxy-3-methylglutaryl coenzyme A reductase localization in rat liver peroxisomes and microsomes of control and cholestyramine-treated animals: quantitative biochemical and immunoelectron microscopical analyses.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a key regulatory enzyme involved in cholesterol biosynthesis, has recently been reported to be present in rat liver peroxisomes (Keller, G.A., M.C. Barton, D.J. Shapiro, and S.J. Singer, 1985, Proc. Natl. Acad. Sci. USA, 82:770-774). Immunoelectron labeling of ultrathin frozen sections of normal liver, using two monoclonal antibodies to purified rat liver microsomal HMG-CoA reductase, indicated that the enzyme is present in the matrix of peroxisomes. This study is a quantitative biochemical and immunoelectron microscopical analysis of HMG-CoA reductase in rat liver peroxisomes and microsomes of normal and cholestyramine-treated animals. Cholestyramine treatment produced a six- to sevenfold increase in the specific activity of peroxisomal HMG-CoA reductase, whereas the microsomal HMG-CoA reductase specific activity increased by about twofold. Using a computer program that calculates optimal linear combinations of marker enzymes, it was determined that between 20 and 30% of the total reductase activity was located in the peroxisomes of cholestyramine-treated animals. Less than 5% of the reductase activity was present in peroxisomes under control conditions. Quantitation of the immunoelectron microscopical data was in excellent agreement with the biochemical results. After cholestyramine treatment there was an eightfold increase in the density of gold particles per peroxisome, and we estimate about a threefold increase in the labeling of the ER.

Animals↗