| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effect of dietary oils, cholesterol and antioxidant vitamin supplementation on liver microsomal fluidity and xenobiotic-metabolizing enzymes in rats Lutz, M., S. Bonilla, et al. (1998), Ann Nutr Metab 42(6): 350-9. Abstract: This study was undertaken to compare the effects of four oils: corn (C), olive (O), hazelnut (H) or fish (F), and the intake of two supplements: cholesterol, 1% (Ch) or dl-alpha-tocopherol acetate, 500 mg/kg, and beta-carotene, 30 mg/kg (V), on liver microsomal fluidity, cyt P450 content and aniline hydroxylase (AH), aminopyrine-N-dimethylase (AND) and UDP-glucuronyltransferase (UDP-GT) activities. Male Sprague-Dawley rats (n = 6/group) were fed semipurified diets containing 15% oil, without or with Ch or V, for 20 days. Dietary intake and feed efficiency were lower in rats fed F. Relative liver weight was higher in animals fed F, similar in O and H, and lower in the group fed C. The intake of V increased feed intake in C+V group and decreased the relative liver weight of F+V group, which also decreased with the intake of F+Ch. Ch intake increased the relative liver weight in all groups consuming vegetable oils. Cyt P450 content was higher in rats fed F. Decreased cyt P450 content was observed in C+Ch and F+Ch groups, while it augmented in H+Ch group. Mixture V increased cyt P450 in rats fed C+V, F+V and O+V. The highest membrane fluidity was observed in rats fed F. Fluidity was also higher in group H versus O or C. The intake of Ch decreased microsomal fluidity in all groups, while V induced an increase in microsomal fluidity in group O+V. Rats fed F exhibited higher enzyme activities. AND activity increased with V only in rats fed H+V, while AH activity increased with V intake in groups F+V and O+V. In the C+V group, fluidity was not affected by V, while the cyt P450 content and UDP-GT activity increased. The O+V group exhibited lower UDP-GT activity and higher fluidity and cyt P450 content. The activity of AH decreased in groups F+Ch and C+Ch. UDP-GT activity was higher in rats fed F. It diminished after the intake of Ch in H+Ch and F+Ch. These results indicate that although AH and AND act in the same microsomal metabolic pathway, their localization into the membrane may be determinant of their activity and the response to dietary lipids. It is shown that F intake exerts the most significant effects upon liver microsomal properties, e.g. higher fluidity, cyt P450 content and enzymatic activities, an effect that prevails over the intake of the supplements tested. |
| Effect of dietary omega-3 eicosapentaenoic acid supplements on cholesteryl ester transfer from HDL in cholesterol-fed rabbits Sugano, M., N. Makino, et al. (1997), Biochim Biophys Acta 1346(1): 17-24. Abstract: We investigated the reactivities of cholesteryl ester transfer protein (CETP) in Japanese white rabbits fed either a low-cholesterol diet containing 0.1% cholesterol (Control group) or a diet containing 0.1% cholesterol plus 17.5% omega-3 eicosapentaenoic acid (omega-3 20:5, EPA) of 4.5% (w/w) total lipid (EPA group) for 6 weeks. The plasma total and LDL cholesterol levels and aortic cholesterol content were all significantly higher in the EPA group than in the control group. The aortic cholesterol content significantly correlated with LDL cholesterol (r = 0.81). HDL cholesterol levels tended to be lower in the EPA group compared with control group, which was not statistically significant. The plasma VLDL cholesterol levels did not differ significantly between the groups. In addition, no significant differences were observed in the plasma CETP activity or lecithin:cholesterol acyltransferase (LCAT) activity between the groups. However, the cholesteryl ester (CE) mass transfer from fractionated HDL in the EPA group to excess VLDL and/or LDL as acceptors by purified CETP increased significantly compared with the control group, even if the acceptors were fractionated from either the EPA or the control group. Fatty acid analyses of CE showed that the omega-3 18:3, 20:4 or omega-3 20:5 fatty acid acyl groups in CE of HDL were significantly more transferred to apo B-containing lipoproteins compared with the 14:0,16:0, 18:0, 18:1 or 18:2 fatty acid acyl groups in CE of HDL during the incubation period. The amount of CE in HDL containing omega-3 18:3 and omega-3 20:5 fatty acid acyl groups was greater, while the amount of CE containing 18:2 fatty acid acyl groups was smaller in the EPA group than in the control group. These results show that although CETP itself did not change, the transfer of CE in HDL to apo B-containing lipoproteins by CETP increased in the rabbits fed a diet containing EPA as the HDL is modified by the diet, which may partly explain why atherogenicity was thus found to progress in the rabbits fed a cholesterol plus EPA diet. |
| Effect of dietary omega-3 fatty acids and chronic ethanol consumption on reverse cholesterol transport in rats Marmillot, P., M. N. Rao, et al. (2000), Metabolism 49(4): 508-12. Abstract: We previously showed that chronic ethanol feeding leads to a decrease of apolipoprotein E (apoE) in high-density lipoprotein (HDL), whereas supplementing this diet with 2.8% of total dietary calories as omega3-fatty acids (omega3FAs) restores HDL-apoE to the control values. Since HDL containing apoE plays a major role in reverse cholesterol transport (RCT), we measured the effects chronic ethanol intake and omega3-FAs on RCT in the present study. Four groups of rats, control normal fat (CN), alcohol-normal fat (AN), control omega3FA fat (CF), and alcohol-omega3FA fat (AF), were fed their respective diets for 8 weeks, after which hepatocytes and HDLs from each group were evaluated for RCT capacity (cholesterol efflux from macrophages and uptake by liver cells). Compared with the control diet (CN), chronic ethanol (AN) feeding inhibited the cholesterol efflux capacity of HDL by 21% (P <.01), whereas omega3FA feeding (2.8% of total dietary calories) stimulated this capacity by 79% (P <.01) and 25% (P <.01) in CF and AF rats, respectively. With respect to cholesterol uptake by the liver, there were no significant 3-way or 4-way interactions between the 4 factors, HDL-alcohol, HDL-fish oil, hepatocyte-alcohol, and hepatocyte-fish oil. The main effects for HDL-alcohol, HDL-fish oil, and hepatocyte-alcohol were all highly significant (P =.0001.0001, and.007, respectively). There was a significant HDL-alcohol and HDL-fish oil interaction (P =.0001). Hepatocyte-alcohol was not a factor in any 2-way interactions. Our study indicates no evidence of an interaction between the effects of omega3FAs and the effects of alcohol on hepatocytes in terms of RCT function. Thus, feeding as little as 2.8% of the total dietary calories as omega3FA not only restored the impaired RCT function of HDL caused by chronic ethanol intake, but also enhanced by severalfold the ability of HDL to promote RCT even in normal animals. |
| Effect of dietary oxidized cholesterol on azoxymethane-induced colonic preneoplasia in mice Kendall, C. W., M. Koo, et al. (1992), Cancer Lett 66(3): 241-8. Abstract: The effect of cholesterol and oxidized cholesterol on azoxymethane-induced colonic preneoplasia was evaluated in C57BL/6J and BALB/cJ mouse strains. Mice were fed either a control AIN 76 semisynthetic diet or the control diet supplemented with 0.1% or 0.3% cholesterol, or 0.1% or 0.3% oxidized cholesterol for an 8-week period. For the first 4 weeks of the experiment, mice received weekly injections of azoxymethane (5 mg/kg body weight). Dietary cholesterol increased fecal concentrations of neutral and acid sterols. A dose-response relationship was observed in both mouse strains between the level of dietary cholesterol or oxidized cholesterol and formation of preneoplastic aberrant crypt foci. Enhanced cell proliferation along with alterations in several crypt morphometric parameters were also observed. These anomalies were enhanced to a greater extent by oxidized cholesterol. This data shows a very strong effect of cholesterol in enhancing the development of preneoplastic lesions in chemically induced cells. It also demonstrated that the state of oxidation of cholesterol influences colonic preneoplasia. This factor has been overlooked in previous animal experiments. |
| Effect of dietary proteins on the blood level of cholesterol Kalamkarova, O. M., T. A. Iatsyshina, et al. (1991), Vopr Pitan(3): 9-16. |
| Effect of dietary supplementation with glucomannan on plasma total cholesterol and low density lipoprotein cholesterol in hypercholesterolemic children Martino, F., E. Martino, et al. (2005), Nutr Metab Cardiovasc Dis 15(3): 174-80. Abstract: AIM: This paper evaluates the effect of the adjunct of the hydrosoluble fiber glucomannan to a Step-One-Diet in 40 plasma hypercholesterolemic children, during a randomized controlled trial, to reduce plasma cholesterol. METHODS: All the subjects recruited underwent an 8-week run in diet period; a Step-One-Diet was prescribed. After that, they were randomly allocated to one of two groups: Step-One-Diet only (control), and Step-One-Diet plus glucomannan in gelatine capsules. After another 8 weeks of treatment, the results were compared within and between the two groups. RESULTS: Glucomannan treated group showed decreased values in plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) vs. control group after 8 weeks of treatment. The percentage decrease showed a statistically significant difference between sex groups. Decreases were observed in favor of female vs. male children in TC (24% vs. 9%) and LDL-C (30% vs. 9%). CONCLUSIONS: These results suggest that glucomannan may represent a rationale adjunct to diet therapy in primary prevention in high risk hypercholesterolemic children. |
| Effect of dietary trans fatty acids on high-density and low-density lipoprotein cholesterol levels in healthy subjects Mensink, R. P. and M. B. Katan (1990), N Engl J Med 323(7): 439-45. Abstract: BACKGROUND. Fatty acids that contain a trans double bond are consumed in large amounts as hydrogenated oils, but their effects on serum lipoprotein levels are unknown. METHODS. We placed 34 women (mean age, 26 years) and 25 men (mean age, 25 years) on three mixed natural diets of identical nutrient composition, except that 10 percent of the daily energy intake was provided as oleic acid (which contains one cis double bond), trans isomers of oleic acid, or saturated fatty acids. The three diets were consumed for three weeks each, in random order. RESULTS. On the oleic acid diet, the mean (+/- SD) serum values for the entire group for total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were 4.46 +/- 0.66. 2.67 +/- 0.54, and 1.42 +/- 0.32 mmol per liter (172 +/- 26, 103 +/- 21, and 55 +/- 12 mg per deciliter), respectively. On the trans-fatty-acid diet, the subjects' mean HDL cholesterol level was 0.17 mmol per liter (7 mg per deciliter) lower than the mean value on the diet high in oleic acid (P less than 0.0001; 95 percent confidence interval, 0.13 to 0.20 mmol per liter). The HDL cholesterol level on the saturated-fat diet was the same as on the oleic acid diet. The LDL cholesterol level was 0.37 mmol per liter (14 mg per deciliter) higher on the trans-fatty-acid diet than on the oleic acid diet (P less than 0.0001; 95 percent confidence interval, 0.28 to 0.45 mmol per liter) and 0.47 mmol per liter (18 mg per deciliter) higher on the saturated-fat diet (P less than 0.001; 95 percent confidence interval, 0.39 to 0.55 mmol per liter) than on the oleic acid diet. The effects on lipoprotein levels did not differ between women and men. CONCLUSIONS. The effect of trans fatty acids on the serum lipoprotein profile is at least as unfavorable as that of the cholesterol-raising saturated fatty acids, because they not only raise LDL cholesterol levels but also lower HDL cholesterol levels. |
| Effect of different dietary levels of Yucca schidigera powder on the performance, blood parameters and egg yolk cholesterol of laying quails Kaya, S., Z. Erdogan, et al. (2003), J Vet Med A Physiol Pathol Clin Med 50(1): 14-7. Abstract: A total of 135 laying quails (Coturnix coturnix japonica), 9 weeks old, were divided into three dietary treatment groups. Three replicates were assigned to each treatment group consisting of 15 birds per cage. The diet was supplemented with 0, 100 and 200 ppm Yucca schidigera powder and given ad libitum to the quails for a period of 14 weeks. Body weight, egg production, feed consumption and feed efficiency were not different due to dietary treatments among the groups. Increased egg weight was determined in the control group. Yucca powder supplementation decreased serum glucose, cholesterol triglyceride level in laying quails. Serum total protein concentration was not changed by dietary treatments but albumin level was decreased in quails fed 100 ppm yucca powder. Egg yolk cholesterol concentration was not significantly different among the groups but tended to decline (11.5%) as a result of yucca supplementation. Red Blood Cell (RBC) and White Blood Cell (WBC) counts, packed cell volume (PCV), mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) were not affected by supplementation of yucca powder. However, haemoglobin (HB) concentration was slightly increased and mean corpuscular haemoglobin concentration (MCHC) was significantly increased by 200 ppm yucca powder supplementation to the diet. |
| Effect of different kinds of dietary casein on blood cholesterol and triglycerides in pair fed rats Guermani, L., C. Villaume, et al. (1992), Nutrition 8(2): 101-4; discussion 110-1. Abstract: After casein intake, serum cholesterol levels are dependent on many experimental conditions in rats. The effect of the method of casein preparation was assessed in Wistar rats pair-fed for 4 wk with three identical diets differing only by the type of casein used. Compared with dietary casein and Na caseinate, ingestion of lipid- and vitamin-free casein resulted in higher liver weights (4.35 +/- 0.23 vs. 3.89 +/- 0.30 and 3.90 +/- 0.25 g) and fasting serum cholesterol levels (0.55 +/- 0.13 vs. 0.49 +/- 0.09 and 0.44 +/- 0.09 g/L). Compared with the two other casein diets, ingestion of Na caseinate produced the lowest fasting serum triglyceride levels (0.62 +/- 0.13 vs 0.74 +/- 0.12 and 0.73 +/- 0.13 g/L). Peptic digestibility of caseins used might be a regulating factor of serum cholesterol levels in Wistar rats. |
| Effect of different olive oils on bile excretion in rats fed cholesterol-containing and cholesterol-free diets Krzeminski, R., S. Gorinstein, et al. (2003), J Agric Food Chem 51(19): 5774-9. Abstract: The mechanism of the hypocholesterolemic effect of olive oils was investigated in 60 Wistar rats adapted to cholesterol-containing and cholesterol-free diets. The rats were divided in six diet groups of 10. The control group was fed only basal diet (BD), which contained wheat starch, casein, cellulose, and mineral and vitamin mixtures. For the five other groups, 10 g/100 g virgin (virgin group) or lampante (lampante group) olive oils, 1 g/100 g cholesterol (chol group), or both cholesterol and oil (chol/virgin and chol/lampante groups) were added to the BD. The experiment lasted 4 weeks. Before and after the experiment the bile was collected, and its flow and biliary bile acids and cholesterol concentrations were registered. Plasma lipids, liver cholesterol, plasma antioxidative potential (TRAP), fecal output, fecal bile acids, and fecal cholesterol excretion were measured. Groups did not differ before the experiment. After the experiment significant hypocholesterolemic and antioxidant effects were registered mainly in groups of rats fed cholesterol-containing diets supplemented with both olive oils (chol/virgin and chol/lampante). Significant increases in the bile flow and in the bile cholesterol and bile acids concentrations were observed (19.2% and 16.9%, 30.5% and 18.2%, and 79.6% and 45.6% for the chol/virgin and chol/lampante groups, respectively). Also, significant increases of the fecal output and fecal excretion of bile acids and cholesterol in rats of these groups were found. In conclusion, olive oils positively affect plasma lipid metabolism. The hypocholesterolemic effect of olive oils is genuine and is most likely mediated through increases in bile flow and biliary cholesterol and bile acids concentrations and subsequent increases in their fecal excretion. |
| Effect of different phospholipid-cholesterol membrane compositions on liposome-mediated formation of calcium phosphates Skrtic, D. and E. D. Eanes (1992), Calcif Tissue Int 50(3): 253-60. Abstract: The present report compares the effects of different membrane phospholipid (PL)-cholesterol compositions on the kinetics of liposome-mediated formation of calcium phosphates from metastable solutions (2.25 mM CaCl2; 1.5 mM KH2PO4) at 22 degrees C, pH 7.4 and 240 mOsm. In most experiments, the liposomes were composed of 7:2:X mixtures of phosphatidylcholine (PC), neutral or acidic phospholipids, and cholesterol (Chol, X = 0, 10, 35, or 50 mol%). The neutral phospholipids (NPL) examined, in addition to PC, were phosphatidylethanolamine (PE) and sphingomyelin (Sph), and the acidic phospholipids (APL) examined were dicetylphosphate (DCP), dioleolylphosphatidylglycerol (DOPG), dioleolylphosphatidic acid (DOPA), phosphatidylserine (PS) and phosphatidylinositol (PI). The 7:2:X liposomes did not initiate mineralization in metasable external solutions per se or, with the exception of DOPA, show extensive Ca-PL binding. However, solution Ca2+ losses due to precipitation occurred when the liposomes were encapsulated with 50 mM KH2PO4 and made permeable to external Ca2+ with X-537A. The extent of these Ca2+ losses was sensitive to both the phospholipid and Chol makeup of the membrane. Moderate-to-extensive intraliposomal precipitation occurred in all 7PC:2APL and 7PC:2NPL liposomes containing 0 or 10 mol% Chol. In contrast, at 50 mol% Chol, mineralization inside all liposomes was negligible. The only significant discriminating effect on internal mineralization among the different phospholipids was observed at 35 mol% Chol, where mineral accumulations ranged from negligible to moderate. At 0 or 10 mol% Chol, extraliposomal precipitation was extensive in all but DOPA- and PS-containing liposomes.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effect of different varieties of pectin and guar gum on plasma, hepatic and biliary lipids and cholesterol gallstone formation in hamsters fed on high-cholesterol diets Trautwein, E. A., A. Kunath-Rau, et al. (1998), Br J Nutr 79(5): 463-71. Abstract: The effect of high- (hePE) and low- (lePE) esterification pectin and high- (hvGG) and low-(lvGG) viscosity guar gum on plasma, hepatic and biliary lipids and on prevention of cholesterol gallstones was investigated in male golden Syrian hamsters (Mesocricetus auratus). Hamsters were fed on cholesterol-rich (4 g/kg), gallstone-inducing diets for 6 weeks. The diets were supplemented with 80 g hePE, lePE, hvGG or lvGG/kg or 80 g additional cellulose/kg. No significant differences in plasma total cholesterol and triacylglycerol concentrations between hvGG and lvGG and the gallstone-inducing or cellulose-enriched diets were observed. The hePE diet produced a 16% (non-significant) reduction in total plasma cholesterol but significantly decreased the plasma triacylglycerol level by 45%. The lePE diet caused only minor changes in plasma lipids. Hepatic cholesterol concentrations were significantly higher in hamsters fed on hvGG, lvGG, hePE or lePE primarily due to the accumulation of esterified cholesterol. Supersaturated bile samples, with lithogenic indices ranging from 1.6 to 2.0, were determined with all diets. The hePE and lePE diets slightly altered the bile acid profile by increasing glycocholic acid and decreasing taurochenodeoxycholic acid concentrations resulting in a higher cholic:chenodeoxycholic acid ratio. Cholesterol gallstone formation was not substantially inhibited by the two varieties of pectin and guar gum. The hvGG, lvGG, hePE and lePE diets did not alter faecal weight and caused only minor increases in faecal bile acid excretion. In general, the present findings demonstrate that dietary pectins and guar gums had only minor effects on cholesterol metabolism and did not prevent cholesterol gallstone formation in this hamster model. Possible explanations for this lack of a distinct response to pectin and guar gum are discussed. |
| Effect of diltiazem on cholesterol and phospholipid content and intensity of free radical oxidation process in plasma membranes of cardiomyocytes and blood cells in experimental hypercholesterolemia Vasilinchuk, N. N. (2004), Ukr Biokhim Zh 76(2): 80-6. Abstract: Changes of lipid structure and function in membranes of cardiomyocytes and blood cells of rabbits were investigated under the effect of experimental hypercholesterolemia and calcium antagonist diltiazem influence. The activity of peroxide oxidizing of lipids (POL) and protein in membrane of sarcolemma, blood cells and serum, and activity of the same enzymes of antioxidant system--catalase (CAT) and superoxide dismutase (SOD) were studied as well. The research marks that diltiazem was manifested by activation of antioxidant system in cardiomyocytes and membrane sarcolemma, normalization of its lipid structure and by the decrease of the content of products POL and oxidizing of protein. |
| Effect of dimethylsulfoxide on sphingomyelinase activity and cholesterol metabolism in Niemann-Pick type C fibroblasts Scalco, F. B., R. Giugliani, et al. (1999), Braz J Med Biol Res 32(1): 23-8. Abstract: Niemann-Pick type C (NPC) fibroblasts present a large concentration of cholesterol in their cytoplasm due to a still unidentified deficiency in cholesterol metabolism. The influence of dimethylsulfoxide (DMSO) on the amount of intracellular cholesterol was measured in 8 cultures of normal fibroblasts and in 7 fibroblast cultures from NPC patients. DMSO was added to the fibroblast cultures at three different concentrations (1, 2 and 4%, v/v) and the cultures were incubated for 24 h. Sphingomyelinase activity was significantly increased in both groups of cells only when incubated with 2% DMSO (59.4 +/- 9.1 and 77.0 +/- 9.1 nmol h-1 mg protein-1, controls without and with 2% DMSO, respectively: 47.7 +/- 5.2 and 55.8 +/- 4.1 nmol h-1 mg protein-1. NPC without and with 2% DMSO, respectively). However, none of the DMSO concentrations used altered the amount of cholesterol in the cytoplasm of NPC cells (0.704 +/- 0.049, 0.659 +/- 0.041, 0.688 +/- 0.063 and 0.733 +/- 0.088 mg/mg protein, without DMSO, 1% DMSO, 2% DMSO and 4% DMSO, respectively). This finding suggests that sphingomyelinase deficiency is a secondary defect in NPC and shows that DMSO failed to remove the stored cholesterol. These data do not support the use of DMSO in the treatment of NPC patients. |
| Effect of diosgenin on biliary cholesterol transport in the rat Thewles, A., R. A. Parslow, et al. (1993), Biochem J 291 (Pt 3): 793-8. Abstract: Biliary cholesterol output in rats was stimulated over 3-fold by feeding diosgenin for 5 days, whereas biliary outputs of phospholipid and bile salts were not changed by diosgenin feeding. Isolating and perfusing the liver without bile salts resulted in a rapid and substantial decrease in biliary bile salt output; bile salt depletion abolished the diosgenin-induced increment in biliary cholesterol output, showing that the diosgenin-elevated biliary cholesterol output was bile-salt-dependent. Diosgenin treatment also produced a significant decrease in biliary alkaline phosphodiesterase I. Fresh bile obtained from control and diosgenin-fed rats was subjected to gel-permeation chromatography in order to separate different-sized biliary cholesterol carriers. Two major peaks of cholesterol were eluted, with cholesterol also being eluted between the peaks. The cholesterol peak eluted at the lower molecular mass (20-30 kDa) was observed in all bile samples. The higher-molecular-mass peak, which was eluted at the void volume, was not observed in all biles; control biles contained very little high-molecular-mass form of cholesterol, whereas biles from the diosgenin group contained up to 47% of cholesterol in the high-molecular-mass fraction. Diosgenin treatment produced a range of elevated biliary cholesterol values which positively correlated with the proportion of cholesterol contained in the high-molecular-mass fraction (r = 0.98). The results show that diosgenin induced a marked bile-salt-dependent increase in biliary cholesterol output and a shift in biliary cholesterol transport to higher-molecular-mass structures. |
| Effect of drugs on cholesterol crystallization in an artificial bile model and relation of this effect to drug binding to albumin Smidkova, M., M. Spundova, et al. (2003), Fundam Clin Pharmacol 17(3): 331-9. Abstract: Substances that can affect the crystallization of cholesterol from human bile and consequently the gallstone formation have been given considerable attention. We improved the model system for testing cholesterol crystallization-affecting activity (promoting or inhibiting) of substances and used it for some drugs that are excreted into bile. Besides other factors natural lipid-protein complexes isolated from the native human bile have been shown to be responsible for nucleation and fast crystal growth in cholesterol supersaturated model bile. Artificial lipid-protein complex of taurolithocholate, human serum albumin and Ca2+ (TLTC-HSA-Ca2+) exhibited a lower crystallization activity than both the artificial lipid-protein complexes of taurodeoxycholate, human serum albumin and Ca2+ and the lipid-protein complex isolated from native human bile. The model bile supplemented with this artificial lipid-protein complex (TLTC-HSA-Ca2+) formed a convenient system for testing of various substances (drugs) for their crystallization-affecting activity. From the 20 tested drugs, which could occur at least in small amounts in human bile, the highest crystallization-promoting activity was found for complexes with ampicillin, butorphanol and colchicine. Complexes with tetracycline, thioridazine and doxycycline were the strongest inhibitors. The drugs, which had some effect on cholesterol crystallization, affected somehow the artificial lipid-albumin complex by displacing its components. Interactions of different drugs with HSA and its artificial complexes with the conjugated bile salt and Ca2+ ions were followed by absorption spectroscopy to observe displacement interactions. On the basis of these experiments we could classify drugs into four groups which differ by their effects on spectral characteristics of complexes. |
| Effect of drugs which inhibit cholesterol synthesis on syncytia formation in vero cells infected with measles virus Malvoisin, E. and F. Wild (1990), Biochim Biophys Acta 1042(3): 359-64. Abstract: We found that nontoxic doses of two inhibitors of cholesterol synthesis, namely W-7 and cerulenin, delayed syncytia formation in vero cells infected with measles virus. To correlate syncytia formation and lipidic membrane changes induced by these drugs, we labelled cell lipids with 14Cacetate. Measles virus infection increased the incorporation of radiolabel into fatty acids, triacylglycerol, cholesterol ester, and decreased its incorporation into cholesterol and 1,2-diacylglycerol. The ratios phosphatidylcholine/sphingomyelin and free cholesterol/lanosterol-dihydrolanosterol also decreased during the infection. W-7 and cerulenin greatly altered lipid metabolism. Both decreased the phosphatidylcholine to sphingomyelin and the cholesterol to lanosterol-dihydrolanosterol ratios. Z-D-Phe-L-Phe-L-Gly, a tripeptide which corresponds to the N-terminal sequence of the viral fusion protein (responsible for syncytia formation) and which inhibits virus-induced cell fusion without affecting virus synthesis also perturbed cholesterol metabolism. The tripeptide reversed the phosphatidylcholine to sphingomyelin ratio in infected cells. At non-toxic doses, W-7 inhibited the synthesis of infectious virus. Cerulenin which inhibited strongly the lipid synthesis did not. Finally, the well characterized inhibitors of cholesterol synthesis, mevinolin, ketoconazole and miconazole were shown to inhibit the syncytia formation. We conclude that the inhibition of syncytia by W-7 and cerulenin is associated with their capacity to alter the cholesterol metabolism, whereas the antiviral effect of W-7 does not seem related to this capacity. |
| Effect of E5324, a novel inhibitor of acyl-CoA:cholesterol acyltransferase, on cholesteryl ester synthesis and accumulation in macrophages Kogushi, M., H. Tanaka, et al. (1995), Jpn J Pharmacol 68(2): 191-9. Abstract: The in vitro potencies of a novel inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), E5324 (n-butyl-N'-2-3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy-6- methylphenylurea), were studied. E5324 was found to be a potent ACAT inhibitor in microsomes from a various tissues and in cultured cell homogenate, with IC50 values in the range of 0.044 to 0.19 microM. The kinetic study on E5324 showed that the inhibition of rat intestine ACAT was competitive with respect to oleoyl CoA. E5324 inhibited 3Holate incorporation into cholesteryl 3Holeate in phorbol ester-treated THP-1 cell lines (IC50 = 0.44 microM). The rate of 3Holeate incorporation into phospholipids and triglycerides was not affected by E5324. In an experiment with 3Hcholesterol as the substrate for ACAT, E5324 also inhibited 3Hcholesteryl ester synthesis (IC50 = 0.41 microM). Furthermore, E5324 prevented accumulation of both esterified and total cholesterol in acetyl low density lipoprotein-loaded THP-1 cells. These results indicate that E5324 is a potent and selective ACAT inhibitor and prevents cholesteryl ester accumulation in macrophages. |
| Effect of early infancy dietary lipid composition on plasma lipoprotein cholesterol and low-density lipoprotein receptor activity Mize, C. E. and R. Uauy (1991), Ann N Y Acad Sci 623: 455-6. |
| Effect of efonidipine hydrochloride (NZ-105), a new dihydropyridine calcium antagonist, on the experimental atherosclerosis in cholesterol-fed rabbits Toyoda, K., M. Kitahara, et al. (1994), Nippon Yakurigaku Zasshi 103(5): 231-9. Abstract: We studied the effect of efonidipine hydrochloride NZ-105:(+-)-2-benzyl(phenyl)aminoethyl 1,4-dihydro-2,6-dimethyl-5- (5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridine-carboxylate hydrochloride ethanol, a newly synthesized dihydropyridine calcium antagonist, on atherosclerosis in 1% cholesterol-fed rabbits. NZ-105 (10, 30 and 100 mg/kg) was orally administered to the animals twice a day for 10 weeks. NZ-105 did not cause any significant change in the plasma lipid levels. The area of atherosclerotic lesion was reduced by 37% (P < 0.05) in the aortic arch and by 54% (P > 0.05) in the thoracic aorta of rabbits administrated 100 mg/kg of NZ-105. The content of cholesterol ester in the aorta was also reduced by 64% (P < 0.05) in the aortic arch and by 73% (P > 0.05) in the thoracic aorta. These results suggest that NZ-105 may suppress the development of atherosclerosis without affecting the plasma lipids. |