Cholesterol Articles and Abstracts

For medical practitioners and the general public - Cholesterol Journal Article Catalog.

Cholesterol Journal Articles



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A comparative study of efficacy of tibolone and simvastatin on atherosclerosis in ovariectomized cholesterol-fed rabbits
Cui, Y., D. Zhao, et al. (2005), Maturitas 50(4): 337-43.
Abstract: BACKGROUND: After menopause women are more susceptible to coronary heart disease due to increased risk of atherosclerosis. Tibolone (Livial) is an innovative synthetic steroid analogue for the treatment of postmenopausal climacteric symptoms including atherosclerosis, but the mechanisms of its effect are still unclear. The present study investigated the effect of tibolone and simvastatin on atherosclerosis and the expression of both estrogen receptor A (ERA) and LDL receptor (LDLR) mRNA in ovariectomized cholesterol-fed rabbits. METHODS: Fifty New Zealand white rabbits were included for the study. Of them, 40 underwent bilateral ovariectomy and the other 10 were sham-operated. The sham-operated group only received atherogenic diet (group SC) and the ovariectomized rabbits were divided into 4 groups of 10 each, with group N received normal diet, group C received atherogenic diet, group T received atherogenic diet and tibolone (2.5 mg/day) and group SI received atherogenic diet and simvastatin (20 mg/day). After 12 weeks of the treatments, the animals were euthanized and the extent of thoracic aortic atherosclerosis was measured morphologically and the level of ERA and LDLR mRNA in heart and liver was determined by real-time RT-PCR. RESULTS: The extent of atherosclerosis in the thoracic aorta was 0.75+/-0.24 for group C, 0.56+/-0.27 for group SC, almost 0 for group N, 0.10+/-0.02 for group T and 0.09 +/-0.08 for group SI (P<0.01; groups T versus C, T versus SC, SI versus C, SI versus SC). The relative copies of ERA at group C, SC, N, T and SI were 0.29, 0.53, 0.46, 0.85 and 0.30, respectively in heart and 0.32, 0.51, 0.49, 0.68 and 0.30, respectively in liver; the relative copies of LDLR at group C, SC, N, T and SI were 0.22, 0.24, 0.33, 0.27 and 0.23, respectively in heart and 0.68, 0.93, 1.52, 1.27 and 0.88, respectively in liver. CONCLUSION: Both tibolone and simvastatin prevented the atherosclerosis in ovariectomized cholesterol-fed rabbits and this effect was associated with up-regulation of ERA and LDLR expression by tibolone but not by simvastatin.

A comparative study of the effects of cholesterol and sclareol, a bioactive labdane type diterpene, on phospholipid bilayers
Kyrikou, I., A. Georgopoulos, et al. (2005), Chem Phys Lipids 133(2): 125-34.
Abstract: Sclareol (labd-14-ene-8,13-diol) is a highly water-insoluble molecule that belongs to the labdane type diterpenes and is characterized as a biologically active molecule, due to its cytotoxic and cytostatic effects against human leukemic cell lines. A superimposition study between sclareol and cholesterol, based on their corresponding hydrophobic and polar molecular segments calculated from their lipophilic profiles, revealed their spatial similarities. This structural similarity between the two molecules prompted us to compare their effects on the structure and stability of phospholipid dipalmitoylphosphatidylcholine (DPPC) membranes. Differential scanning calorimetry (DSC) was applied to compare the thermal changes caused by either cholesterol or sclareol when are incorporated in DPPC bilayers. The results showed that sclareol is incorporated into phospholipid model membranes and mimics the thermal effects of cholesterol especially at concentrations up to X(sclareol)=9.1 mol%. These effects can be summarized as the abolition of pre-transition, lowering of the main phase transition and reduction of the enthalpy change (DeltaH) of the gel to liquid-crystalline phase transition of DPPC bilayers. At concentrations X> or =16.7 mol%, sclareol and cholesterol caused different heterogeneity in lipid bilayers or a reversible transition from a vesicular suspension to an extended peak bilayer network. This different fluidization, exerted by the two molecules at high concentration, may be related to their different stability and the z-average mean diameter of the liposomes they form. Small unilamellar vesicles, prepared by the thin film hydration method showed that DPPC bilayers containing a high concentration of sclareol in equimolar ratio sclareol:cholesterol were unstable, in contrast to the ones containing only cholesterol.

A comparative study of the effects of cholesterol, beta-sitosterol, beta-sitosterol glucoside, dehydroepiandrosterone sulphate and melatonin on in vitro lipid peroxidation
van Rensburg, S. J., W. M. Daniels, et al. (2000), Metab Brain Dis 15(4): 257-65.
Abstract: The free radical scavenging abilities of the structurally related steroids beta-sitosterol, beta-sitosterol glucoside (plant sterols and sterolins), cholesterol, and dehydroepiandrosterone sulphate (DHEAS) were compared with melatonin (an efficient free radical scavenger) in an in vitro system which measures lipid peroxidation of platelet membranes in the presence of iron (Fe2+). Lipid peroxidation is a process whereby cellular membranes are damaged due to the oxidative deterioration of polyunsaturated lipids, which may lead to cell death and disease in living organisms. Substances such as vitamin E protect cellular membranes against oxidative damage due to their chemical structures. The steroids cholesterol, beta-sitosterol, beta-sitosterol glucoside and dehydroepiandrosterone (DHEA) are structurally related to each other. During aging, serum concentrations of DHEA, DHEAS and melatonin decrease, while the concentration of cholesterol tends to increase. The aim of the present study was to compare the role these substances play in lipid peroxidation over a wide concentration range. At concentrations lower than the free iron in the reaction mixture, all the steroids investigated decreased lipid peroxidation. At higher concentrations, cholesterol and beta-sitosterol increased lipid peroxidation, while DHEAS and melatonin continued to decrease lipid peroxidation.

A comparative study of the effects of vegetable oils and cholesterol on enzymes of the mouth and jejunal mucosae
Vavilova, T. P., A. V. Kosarev, et al. (1992), Vopr Pitan(2): 53-6.
Abstract: The influence of sunflower and olive oils and their combination with cholesterol on the activity of lysosomal hydrolases and lipid peroxidation (LPO) in the mucosa of the mouth and jejunum was studied. It was shown that in the presence of cholesterol in the oral mucosa the activity of N-acetylhexosaminidase increased and there was a tendency to decreasing cathepsin D and acetyl esterase activity, and LPO processes were found to be suppressed. Cathepsin D and B activities in the jejunum mucosa increased in response to cholesterol administration. The changes revealed in the activities of N-acetylhexosaminidase, proteinase, acetyl esterase, catalase and glutathione peroxidase in the oral mucosa, as well as cathepsins in the jejunum depend on the character of lipid additives.

A comparative study of three different test diets in change in plasma total cholesterol in young healthy individuals
Arora, R. C., N. Agarwal, et al. (1991), Mater Med Pol 23(4): 296-8.
Abstract: The effect of single dose of three different types of high cholesterol diet on plasma total cholesterol (PTC) in 24 young healthy subjects (male:female = 1:1) aged 15 to 35 years was studied. One group (n1 = 8) was given a butter and milk diet (300 mg cholesterol and 95 g fat). In the first postprandial hour PTC level increased significantly in all but one subject (mean +/- S.D., 4.96 +/- 0.57 m mol/l to 5.61 +/- 0.60 m mol/l, P < 0.005). Second group (n2 = 8) was given a single egg diet (300 mg cholesterol and 6 g fat). In the first hour the PTC level decreased significantly in all but 2 subjects (4.82 +/- 0.58 m mol/l to 4.42 +/- 0.63 m mol/l, P < 0.02). Third group subjects (n2(3) = 8) were given a test diet consisting of crystalline cholesterol with 200 ml milk (1020 mg cholesterol and 14 g fat). The PTC level increased insignificantly. In the first hour in all but 2 subjects (4.94 +/- 0.43 m mol/l to 5.35 +/- 0.88 m mol/l, P > 0.10). In the third postprandial hour the PTC values in all the 3 groups showed a tendency to return to fasting values. Therefore, we conclude that the effect of dietary cholesterol on PTC depends not only on the amount of cholesterol content in the diet, but on the type of diet (cholesterol vehicle) as such and probably also on the fat content of the diet.

A comparative study on blood cholesterol and dietary fat intake between Hong Kong and Cantonese children
Leung, S. S., M. Y. Ng, et al. (1994), Zhonghua Yu Fang Yi Xue Za Zhi 28(4): 199-201.
Abstract: Blood cholesterol level in children aged 7 in Hong Kong (4.59mmol/L) was significantly higher than that in Jiangmen City, Guangdong Province (4.16mmol/L). Duplicate meals were collected from 20 children each in Hong Kong and Jiangmen for chemical analysis of fat intake and fatty acid profile. Results showed daily fat intake was 34.7 g for children in Jiangmen, which was about 30% lower than that in Hong Kong (47.6 g). Fatty acid profile in the diet of Jiangmen children showed a significantly higher polyunsaturated fatty acid saturated fatty acid ratio (0.81 vs 0.69) and linoleic acid/myristic acid ratio (20.73 vs 10.91) than that of Hong Kong children. It suggested dietary mode in a society with rapid developing economy and well-to-do life has changed, and it is necessary to prevent from the damage to health, especially the risk of coronary heart disease, caused by over-nutrition, as early as possible.

A comparison of HDL and LDL cholesterol for prevalent coronary calcification
Allison, M. A. and C. M. Wright (2004), Int J Cardiol 95(1): 55-60.
Abstract: BACKGROUND: Coronary calcification is a marker for coronary atherosclerosis. It has been postulated that high levels of high density lipoprotein cholesterol (HDL-C) are associated with a reduced amount of atherosclerotic disease while previous reports have found a lack of association between low density lipoprotein cholesterol (LDL-C) and coronary calcification (CAC). The purpose of this study was to compare the correlation and predictive power of HDL-C with LDL-C for prevalent coronary calcification. METHODS: A total of 6093 subjects were studied with respect to coronary calcification, serum cholesterol indices, personal health history and body morphology. Analyses consisted of correlation coefficients, logistic regression and sensitivity analysis to determine the strength of association between HDL-C and coronary calcification after controlling for covariates. RESULTS: The correlation between HDL-C and coronary calcium score (CCS) was three times that of LDL-C. Individuals with an HDL-C level <40 mg/dl had significantly higher calcium scores while increases in HDL-C were associated with a significant reduction in risk for the presence of any calcified plaque. Results of multivariate logistic regression revealed that HDL-C is predictive of calcified plaque development independent of LDL-C. Sensitivities and positive predictive values for both HDL-C and LDL-C were low. CONCLUSIONS: Increasing levels of HDL-C were associated with less coronary calcification and a smaller probability of having any calcified disease supporting the antiatherogenic hypothesis for HDL-C. HDL-C predicts the presence of any calcified atherosclerotic plaque independently of LDL-C. However, neither parameter seems suitable as a screening tool for predicting prevalent calcified atheromatous disease.

A comparison of participants and nonparticipants in a worksite cholesterol screening
Hyman, D. J., G. Paradis, et al. (1992), Am J Health Promot 7(2): 137-41.
Abstract: PURPOSE. The purpose of this study is to determine if worksite cholesterol screening reaches only those who are already aware of their cholesterol and interested in lifestyle modification. DESIGN. A voluntary worksite cholesterol screening was conducted followed by a survey of a random sample of nonparticipants. SETTING. A large university worksite was the setting for this study. SUBJECTS. Out of 9,137 university employees, 1,583 attended the voluntary screening, and a random sample of nonparticipants was obtained (n = 154), of which 87% (n = 138) responded. MEASURES. Subjects completed a questionnaire on health behaviors, perceived risk, self-efficacy for diet change, and attention to media messages. A capillary blood cholesterol level was also taken. RESULTS. Nonparticipants were more likely to be male (64% versus 39%) and smokers (17% versus 9%), more likely to exercise, to have had a prior cholesterol measurement (64% versus 49%), and to "know" their cholesterol value (56% versus 26%). The two groups were otherwise similar. Over half (51%) of the participants were receiving their first cholesterol measurement. These subjects were younger, less educated, had less perceived risk, were less attentive to media messages, and more likely to be from a minority group than those individuals who had prior measurements. DISCUSSION. These findings suggest that worksite cholesterol screening does not only reach those already aware of their cholesterols, but also can reach some persons not previously screened or concerned.

A comparison of pseudo-ternary diagrams of aqueous mixtures of Quil A, cholesterol and phospholipid prepared by lipid-film hydration and dialysis
Demana, P. H., N. M. Davies, et al. (2004), J Pharm Pharmacol 56(5): 573-80.
Abstract: Pseudo-ternary diagrams for Quil A, phospholipid (phosphatidylcholine (PC) or phosphatidylethanolamine (PE)) and cholesterol were established in order to identify combinations that result in the formation of immune-stimulating complex (ISCOM) matrices and other colloidal structures produced by these three components in aqueous systems following lipid-film hydration or dialysis (methods that can be used to produce ISCOMs). In addition, the effect of equilibration time (1 month at 4 degrees C) on the structures formed by the various combinations of the three components was investigated. Depending on the ratio of Quil A, cholesterol and phospholipid, different colloidal particles, including ISCOM matrices, liposomes and ring-like micelles, were found irrespective of the preparation method used. In contrast, worm-like micelles were only observed in systems prepared by lipid-film hydration. For samples prepared by dialysis, ISCOM matrices were predominantly found near the Quil A apex of the pseudo-ternary diagram (> 50% Quil A). On the other hand, for samples prepared by lipid-film hydration, ISCOM matrices were predominantly found near the phospholipid apex of the pseudo-ternary diagram (> 50% phospholipid). The regions in the pseudo-ternary diagrams in which ISCOM matrices were observed increased following an extended equilibration time, particularly for samples prepared by lipid-film hydration. Differences were also observed between pseudoternary diagrams prepared using either PE or PC as phospholipids.

A comparison of results for cholesterol in human serum obtained by the Reference Method and by the Definitive Method of the National Reference System for cholesterol
Ellerbe, P., G. L. Myers, et al. (1990), Clin Chem 36(2): 370-5.
Abstract: Here we compare the Reference Method (I) and the Definitive Method (II) for measurement of cholesterol in serum. For pure cholesterol solutions, values by I agree with values by II, but for fresh, frozen, or lyophilized sera, values by I average 1.6% higher than values by II. We conclude that an undetected interference is associated with I. However, the observed difference does not diminish the usefulness of I as an accuracy base for cholesterol measurements, because it is clinically insignificant at present.

A comparison of results of a national cholesterol and blood pressure screening with the NHANES II Study: implications for further emphasis on reducing cardiovascular risk among Americans
Fridinger, F. W., A. W. Jackson, et al. (1992), J Community Health 17(4): 247-57.
Abstract: A comparison was made of serum total cholesterol and blood pressure levels taken from participants in a voluntary national health screening (N = 257,665) in 1988 with estimates for the general U.S. population from the NHANES II Study (1976-80). Although total serum cholesterol and blood pressure levels in the national health screening may be biased due to a higher proportion of females and whites, curvilinear age-related increases in mean total serum cholesterol (peak years 60-69) of approximately the same proportions among "desirable" to "high" classifications, and similar proportional increases in elevated blood pressure readings across age groups, were found in both the voluntary screening and NHANES II population estimates. Within and between gender-comparisons of total cholesterol and blood pressure measures showed greater risk among participants in the present study. The findings suggest that both blood cholesterol and blood pressure levels in the U.S. may not have decreased appreciably in the past decade, and that continued national, state and local public health efforts to modify behaviors related to hypercholesteremia and hypertension are warranted.

A comparison of serum total cholesterol levels and their determinants between the Federal Republic of Germany and the United States
Rehm, J., C. Sempos, et al. (2000), Eur J Epidemiol 16(7): 669-75.
Abstract: Mean serum total cholesterol levels appear to be higher in the Federal Republic of Germany (FRG) than in the United States (US) while coronary heart disease death rates are lower. The study examined possible factors for the difference including possible differences in laboratory methodology. Cross-sectional data from the first two waves of the German National Health Surveys (1984-1986 and 1987-1989; n = 9709) and from the Second National Health and Nutrition Examination Survey (1976-1980; n = 7832) were compared for men and women 25-69 years of age. The influence of age, body mass index, diet, cigarette smoking, education, income, use of oral contraceptives or antihypertensive agents, alcohol consumption and potential differences in laboratory measurement were explored using multiple regression techniques separately for men and women for ages 25-39, 40-59 and 60-69 years of age. Overall ages, unadjusted mean total cholesterol levels were higher in German than US men (6.02 vs. 5.64 mmol/l) and in German than US women (6.04 vs. 5.80 mmol/l) as were HDL cholesterol levels (men: 1.30 vs 1.14 mmol/l; women: 1.65 vs. 1.38 mmol/l). Adjusting for lifestyle factors explained, on the average, 40% of the differences in mean total cholesterol of which half or 20% was accounted for by adjusting for alcohol intake. Adjusting for possible laboratory differences explained, on the average, an additional 30% of the differences. Frequency of alcohol intake was the most important factor in explaining differences in mean HDL cholesterol levels. Adjustment for differences in alcohol intake had negligible effects on reducing the differences in mean non-HDL cholesterol.

A comparison of the behavior of cholesterol and selected derivatives in mixed sterol-phospholipid Langmuir monolayers: a fluorescence microscopy study
Berring, E. E., K. Borrenpohl, et al. (2005), Chem Phys Lipids 136(1): 1-12.
Abstract: Eukaryotic cells require sterols to achieve normal structure and function of their plasma membranes, and deviations from normal sterol composition can perturb these features and compromise cellular and organism viability. The Smith-Lemli-Opitz syndrome (SLOS) is a hereditary metabolic disease involving cholesterol (CHOL) deficiency and abnormal accumulation of the CHOL precursor, 7-dehydrocholesterol (7DHC). In this study, the interactions of CHOL and the related sterols desmosterol (DES) and 7DHC with l-alpha-dipalmitoylphosphatidylcholine (DPPC) monolayers were compared. Pressure-area isotherms and fluorescence microscopy were used to study DPPC monolayers containing 0, 10, 20, or 30 mol% sterol. Similar behavior was noted for CHOL- and DES-containing DPPC monolayers with both techniques. However, while 7DHC gave isotherms similar to those obtained with the other sterols, microscopy indicated limited domain formation with DPPC, indicating that 7DHC packs somewhat differently in DPPC membranes compared to CHOL and DES. These results are discussed in relation to SLOS pathobiology.

A comparison of the effect of medium- vs. long-chain triglycerides on the in vitro solubilization of cholesterol and/or phytosterol into mixed micelles
von Bonsdorff-Nikander, A., L. Christiansen, et al. (2005), Lipids 40(2): 181-90.
Abstract: Despite clinical evidence of the cholesterol-lowering effects of phytosterols, the exact mechanisms involved are still unclear. Displacement of cholesterol by phytosterols from mixed micelles, which is due to their greater hydrophobicity, is one of the hypotheses for the lumenal effects contributing to the reduction of intestinal cholesterol absorption. In this study a dynamic in vitro lipolysis method was used to examine the solubilization behavior of cholesterol and/or phytosterols during lipolysis to probe the efficacy of cholesterol displacement from mixed micelles by phytosterols. The effects of lipid chain length on sterol solubilization were studied by using microcrystalline suspensions containing 17% phytosterol or cholesterol, formulated in long-chain TG (LCT) and medium-chain TG (MCT). When digesting cholesterol-suspended in LCT, the entire cholesterol dose was incorporated into the micellar phase. For the cholesterol formulation suspended in MCT, 50.3% of the initial dose was recovered in the micelles. Under the respective conditions, we observed lower solubilization of phytosterols than of cholesterol (roughly fourfold). Only 25% of the initial phytosterol dose was solubilized from suspensions formulated with LCT, and 13% was solubilized from MCT formulations. Co-administration of phytosterol and cholesterol suspensions showed a significant reduction of cholesterol solubilization, particularly when dosed in MCT, with approximately 25% of the cholesterol dose solubilized. Insignificant amounts of cholesterol were displaced by phytosterols when cholesterol was presolubilized in the mixed micelles. The results show that, compared with LCT, mixed micelles containing MCT lipolysis products have a reduced solubilizing capacity for cholesterol, which adds to the effectiveness of the phytosterols in displacing cholesterol. This suggests potential benefits of using medium chain length lipids in cholesterol-lowering phytosterol products.

A comparison of the effects of cholesterol on CHD mortality in black and white women: twenty-eight years of follow-up in the Charleston Heart Study
Knapp, R. G., S. E. Sutherland, et al. (1992), J Clin Epidemiol 45(10): 1119-29.
Abstract: The relationship between cholesterol and 28-year CHD mortality in women was evaluated in the Charleston Heart Study. Linear, quadratic, and cubic models were investigated using Cox proportional hazards regression analysis. In white women, the linear, quadratic, and cubic terms for cholesterol were significant suggesting an asymmetric J-shaped relationship. In black women, only the linear term in all three models was statistically significant suggesting an increasing CHD mortality rate with increasing cholesterol level. The lack of consistency of results by different statistical analyses in black women make conclusions concerning the nature of the relationship between cholesterol and CHD mortality less strong in black women than in white women. Compared with women having a cholesterol value equal to the mean of the group (241 mg/dl), white women having a cholesterol value one standard deviation above the mean (s = 52.5 mg/dl) had a 60% higher CHD mortality rate (hazard ratio = 1.6, 95% CI: 1.2-2.1). In black women, the estimated hazard ratio for a one standard deviation (s = 47.8 mg/dl) increase in cholesterol is 1.4 (95% CI: 1.03-1.8). The results suggest that the relationship of cholesterol to CHD mortality is different in white and black women. The relationship in white women appears to be curvilinear and represented by an asymmetric curve while the relationship in black women is not curvilinear and the overall pattern of association, while possibly linear, is equivocal.

A comparison of the effects of repeated stressor exposures and corticosterone injections on plasma cholesterol, thyroid hormones and corticosterone levels in rats
Servatius, R. J., J. E. Ottenweller, et al. (1994), Life Sci 55(21): 1611-7.
Abstract: Persistently elevated serum cholesterol (CHOL) levels have been observed in rats given repeated stressor exposures and fed a normal laboratory diet. To determine the relative contribution of persistent hormone changes in the hypothalamic-pituitary-adrenal (HPAA) and thyroid axes to persistent stress-induced CHOL elevations, the present experiment assessed the contribution of persistently elevated corticosterone (CORT) from both endogenous and exogenous sources. Groups of rats were exposed for 7 days to stress sessions (7DS; 40, 2mA tailshocks given over 2 h each day), CORT injections (CI; 10 mg/l ml vehicle/day) or vehicle injections (VI; sesame oil), or served as noninjected, undisturbed controls (CON). In addition, another group of rats were adrenalectomized (ADX). Basal blood samples were drawn for CORT determination on the 1st, 4th, 7th, and 8th experimental days. The blood samples from the 8th day, 22 h after the last stress session or injection were also assayed for CHOL, T3 and T4. The basal CORT levels of both 7DS and CI rats were elevated on the 4th and 7th experimental days. Contrary to expectations, 7 daily exposures to the stress regimen did not persistently alter plasma CORT, CHOL, T3 or T4 levels. The CI rats did exhibit elevated CORT on the 8th experimental day which was accompanied by elevated CHOL levels and suppressed T4 levels. However, elevated CHOL levels were also found in ADX rats and these elevations were accompanied by suppressed T3 levels. These data suggest that persistent CORT elevations are not necessary for persistent plasma CHOL elevations after stressor exposure, but further research is necessary to clarify the role of the HPAA and thyroid axes in stress-induced plasma CHOL elevations.

A comparison of the regulation of de novo cholesterol synthesis by LDL and Lp(a)
Gilligan, S. M. and P. B. Collins (1995), Biochem Soc Trans 23(2): 351S.

A computer model of the gene network of the cholesterol biosynthesis regulation in the cell: analysis of the effect of mutations
Ratushnyi, A. V., V. A. Likhoshvai, et al. (2003), Dokl Biochem Biophys 389: 90-3.

A concept for normal range of serum cholesterol
Usui, T. (1991), Rinsho Byori 39(5): 483-8.
Abstract: The normal range of serum cholesterol is not primarily defined. It largely depends on conditions of respective population such as age, sex and food uptake. Therefore, the reported normal range of respective laboratory differ each other. The upper limit of the normal range used in laboratories on Japan in recent decade is about 240-250 mg/dl, which were obtained statistically from normal persons. On the other hand, another normal range with 220 mg/dl upper limit was proposed after Framingham Study and other clinical studies. Many of clinical doctors are confusing with these two different normal ranges. We must clearly define the normal range whether it is obtained statistically or is used for preventive medicine, when it is presented to doctors.

A conformational analysis study of the interaction of amiodarone and cholesterol with lysophosphatidylcholine
Chatelain, P. and R. Brasseur (1991), Biochem Pharmacol 41(11): 1639-47.
Abstract: The spatial configuration of amiodarone (in both its protonated and neutral forms) and a hydroxylated analog was studied using conformational analysis in a simulated membrane-water environment. The three compounds and cholesterol were studied as isolated molecules and in interaction with lysophosphatidylcholine. The association of the molecules with lysophosphatidylcholine was further characterized by incorporation in a phosphatidylcholine matrix. Calculation of the mean interaction energy, the surface charge density and the hydrophilic and hydrophobic mean molecular areas showed that the protonated form of amiodarone, and to a lesser extent cholesterol form a stable association with lysophosphatidylcholine. This association was further stabilized when incorporated into a phosphatidylcholine matrix so that the mean interaction energy increased to -96.1 kJ/mol (i.e. 60% higher than the mean lipid-lipid energy of interaction). Lysophosphatidylcholine was shown to possess a cone-shaped structure whilst amiodarone was shown to be in the form of an inverted cone. This association of the two cones forms a stable cylindrical structure.


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