| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effect of egg white on serum cholesterol concentration in young women Asato, L., M. F. Wang, et al. (1996), J Nutr Sci Vitaminol (Tokyo) 42(2): 87-96. Abstract: In a previous study we observed favorable effects of egg white on serum lipids in rats and mice. The present study was designed to elucidate these effects in 24 female university students with moderate hypercholesterolemia. About 30% of total protein was supplied with egg white, tofu or cheese. The experiment was conducted for a complete menstruation cycle of each subject. Lipid intake was about 30% of total energy intake. The energy intake of each subject was constant throughout the experiment. Body weight was measured every morning. Daily activity was measured by a pedometer. Blood was withdrawn after an overnight fast on the first, 15th and last days and serum lipids were measured. Body weight was measured every morning. Daily activity was measured by a pedometer. Blood was withdrawn after an overnight fast on the first, 15th and last days and serum lipids were measured. Body weight and daily activity were maintained in all the groups throughout the experiment. The egg white group showed a similar decrease in the total cholesterol (Total-C) concentration but a greater increase of high-density lipoprotein cholesterol (HDL-C) concentration as compared to the tofu group and a greater decrease in Total-C and low-density lipoprotein cholesterol (LDL-C) concentrations and a greater increase in the HDL-C concentration as compared to the cheese group (p < 0.05). The results indicate the favorable effects of egg white in the control of hypercholesterolemia. |
| Effect of elective hospitalization on plasma lipoprotein cholesterol and apolipoproteins A-I, B and Lp(a) Genest, J. J., J. R. McNamara, et al. (1990), Am J Cardiol 65(9): 677-9. |
| Effect of endogenous estrogen on plasma high density lipoprotein and total hydrosulfuryl group in membrane of erythrocyte in cholesterol-fed rats Li, R. Y. (1992), Zhonghua Xin Xue Guan Bing Za Zhi 20(5): 313-4, 325. Abstract: Under a cholesterol load, the effects of endogenous estrogen on plasma high density lipoprotein cholesterol (HDL-C), total hydrosulfuryl (T-SH) group in the membrane of erythrocyte and plasma total cholesterol were observed in female rats with a ovariectomized control group. The results indicate that endogenous estrogen might prevent the rats of atherosclerosis formation by keeping plasma HDL at higher level and increasing in T-SH group in the membrane of erythrocyte, and preventing the increase in total plasma cholesterol. |
| Effect of endotoxin on cholesterol biosynthesis and distribution in serum lipoproteins in Syrian hamsters Feingold, K. R., I. Hardardottir, et al. (1993), J Lipid Res 34(12): 2147-58. Abstract: Infection and inflammation increase serum triglyceride and cholesterol levels in rodents and rabbits. Endotoxin (LPS) has been used as a model of infection and its effects on triglyceride metabolism have been previously characterized. In the present study we demonstrate that both low (100 ng/100 g body weight) and high dose (100 micrograms/100 g body weight) LPS increase serum cholesterol levels in hamsters. The increase in serum cholesterol is first observed 16 h after LPS and persists for at least 24 h. This increase is primarily due to an increase in low density lipoprotein (LDL) cholesterol. High density lipoprotein (HDL) cholesterol levels decrease after LPS treatment. Both low and high dose LPS increase hepatic cholesterol synthesis (low dose 85%, high dose 205%) and total HMG-CoA reductase activity (low dose 2.97-fold, high dose 9.96-fold). However, the proportion of HMG-CoA reductase in the active form is reduced by LPS treatment. Additionally, the mass of HMG-CoA reductase protein in the liver, measured by Western blotting, is increased after LPS. Moreover, LPS increases hepatic HMG-CoA reductase mRNA levels (low dose 3.1-fold, high dose 14.2-fold). The increase in hepatic HMG-CoA reductase mRNA levels is first seen 4 h after LPS and persists for at least 24 h. In contrast, LPS had only minimal effects on hepatic LDL receptor protein and mRNA levels. These results suggest that LPS increases serum cholesterol levels by increasing hepatic cholesterol synthesis. LPS administration decreases apoE mRNA levels in the liver while having no effect on apoA-I mRNA levels. These results suggest that HMG-CoA reductase is a member of a group of hepatic proteins that are positively regulated by inflammatory stimuli (acute phase proteins) while apoE can be considered a negative acute phase protein in hamsters. It is possible that increases in hepatic HMG-CoA reductase provide cholesterol that allows for the increased production of lipoproteins and elevations in serum lipid levels that may be beneficial to the body's host defense. |
| Effect of enduracin on the activity of a cholesterol ester transfer protein in blood plasma of people with hypercholesteremia Gorshkova, I. N., N. G. Kiseleva, et al. (1996), Biull Eksp Biol Med 121(2): 185-7. |
| Effect of epomediol on ethinyloestradiol-induced changes in bile acid and cholesterol metabolism in rats Cuevas, M. J., J. L. Mauriz, et al. (2001), Clin Exp Pharmacol Physiol 28(8): 637-42. Abstract: 1. Epomediol is a terpenoid compound that has been reported to stimulate bile acid synthesis and to reverse 17alpha- ethinyloestradiol-induced cholestasis. The aim of the present study was to investigate the contribution of changes in bile acid and cholesterol metabolism to the protective effects of epomediol in ethinyloestradiol-treated rats. Animals received epomediol for 5 days at 100 mg/kg daily, i.p., ethinyloestradiol for 5 days at 5 mg/kg, s.c., or a combination of both drugs. 2. When compared with control animals, epomediol treatment resulted in a significant increase in bile flow (+42%) and in the secretion of bile acids (+74%) and cholesterol (+42%). Ethinyloestradiol administration caused a significant decrease in bile flow (-43%), bile acid secretion (-37%) and cholesterol secretion (-45%). Bile flow, bile acid secretion and cholesterol secretion were significantly increased in animals receiving ethinyloestradiol plus epomediol compared with ethinyloestradiol-treated rats (+13, +29 and +31%, respectively). 3. Both cholesterol 7alpha-hydroxylase and hydroxy-3- methylglutaryl coenzyme A reductase activities were significantly increased in epomediol-treated rats (+30 and +96%, respectively). Cholesterol 7alpha-hydroxylase activity was significantly reduced by ethinyloestradiol (-22%) and did not differ from control values in animals receiving epomediol plus ethinyloestradiol. Levels of cholesterol 7alpha-hydroxylase mRNA were elevated (+41%) by epomediol, but were not significantly modified by ethinyloestradiol or ethinyloestradiol plus epomediol. 4. It is concluded that epomediol enhances bile acid secretion by increasing the expression of cholesterol 7alpha-hydroxylase. Changes in bile acid metabolism contribute to the effects of epomediol in rats with ethinyloestradiol-induced cholestasis. |
| Effect of ER-27856, a novel squalene synthase inhibitor, on plasma cholesterol in rhesus monkeys: comparison with 3-hydroxy-3-methylglutaryl-coa reductase inhibitors Hiyoshi, H., M. Yanagimachi, et al. (2000), J Lipid Res 41(7): 1136-44. Abstract: Squalene synthase (SQS; EC 2.5.1.21) plays an important role in the cholesterol biosynthetic pathway. We discovered ER-28448, 5-(N-2-butenyl-3-(2-methoxyphenyl)-N-methylamino)-1, 1-penthylidenebis(phosphonic acid) trisodium salt, as a potent and selective inhibitor of SQS. ER-28448 inhibited SQS in rat liver microsome with an IC(50) value of 3.6 nm. We also prepared ER-27856, the tripivaloyloxymethyl ester prodrug of ER-28448. Although less active than ER-28448 in a liver microsome assay, ER-27856 more potently inhibited cholesterol biosynthesis in rat hepatocytes; and ER-27856 orally inhibited de novo cholesterol biosynthesis in Sprague-Dawley rats, with an ED(50) value of 1.6 mg/kg. In HepG2 cells, ER-27856 upregulated low density lipoprotein receptor activity to 2.1 times that of control. A time-course study indicated that the inhibitory effect of ER-27856 on cholesterol biosynthesis in rats continued for up to 8 h. In a study of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMGRIs), atorvastatin actively suppressed cholesterol biosynthesis for 8 h, whereas the effect of pravastatin and simvastatin diminished at 4 and 8 h, respectively. In rhesus monkeys, 4 days of oral administration of ER-27856 lowered plasma total cholesterol (TCHO) more potently than did these HMGRIs. Whereas atorvastatin significantly elevated plasma alanine aminotransferase, a marker of hepatotoxicity, to 3.7 times at 100 mg/kg, ER-27856 increased the level only 1.4 times at 10 mg/kg, at which doses the hypocholesterolemic effect was equivalent. During 28 days of administration, ER-27856 reduced TCHO and non-high density lipoprotein (non-HDL) cholesterol by 72 and 95%, respectively.These results demonstrate that ER-27856 had more potent hypocholesterolemic activity and less hepatotoxic effect than HMGRIs. ER-27856 may contribute to the treatment of hypercholesterolemic patients. |
| Effect of esterified 4-desmethylsterols and -stanols or 4,4'-dimethylsterols on cholesterol and bile acid metabolism in hamsters Trautwein, E. A., C. Schulz, et al. (2002), Br J Nutr 87(3): 227-37. Abstract: 4-Desmethylsterols and -stanols reduce plasma total cholesterol (TC) and LDL cholesterol by inhibition of intestinal cholesterol absorption, while the cholesterol-lowering potential of 4,4'-dimethylsterols is less well defined. The present study aimed to compare the effects of 4-desmethylsterols, -stanols, and 4,4'-dimethylsterols on plasma and hepatic cholesterol, sterol excretion and bile acid metabolism. Male golden Syrian hamsters were fed diets containing 13 g/100 g fat, 008 g/100 g cholesterol and 0 (control), 0.24 or 0.48% (w/w) esterified 4-desmethylsterols (sterols) and esterified hydrogenated 4-desmethylsterols (stanols) from common vegetable oils or esterified 4,4'-dimethylsterols from rice bran oil for 5 weeks. Sterol and stanol esters at the dose of 0.24% were equally effective and significantly (P<0.05) lowered TC by 15%, while 0.24% 4,4-dimethylsterols reduced TC by 10%. Liver total and esterified cholesterol concentrations were significantly (P<0.05) lowered by 40, 22, 43 and 31% in hamsters fed 0.48% sterols, 0.24% stanols, 0.48% stanols or 0.48% dimethylsterols, respectively. Daily faecal bile acid excretion and hepatic cholesterol 7alpha-hydroxylase activity were not altered, indicating that sterols, stanols and dimethylsterols had no effect on the intestinal re-absorption of bile acids or on hepatic bile acid synthesis. Daily excretion of cholesterol was significantly higher in hamsters fed esterified sterols and stanols, but was only slightly increased in those fed dimethylsterols. The results indicate that esterified sterols and stanols were equally effective in lowering plasma TC and LDL cholesterol, while dimethylsterol esters caused a weaker cholesterol-lowering effect. Sterols and stanols achieve their cholesterol-lowering effect by stimulating faecal cholesterol excretion through inhibiting intestinal cholesterol absorption, but do not affect bile acid excretion. Other mechanisms need to be considered to explain the effect on plasma and hepatic cholesterol of dimethylsterols. |
| Effect of estradiol and progesterone on cholesterol 7 alpha-hydroxylase activity in rats subjected to different feeding conditions Chico, Y., O. Fresnedo, et al. (1994), Steroids 59(9): 528-35. Abstract: The regulation of cholesterol 7 alpha-hydroxylase activity by estradiol and progesterone was investigated in liver microsomes isolated from rats fed standard diet, either ad libitum or fasted for 24 h, and diet containing the bile acid sequesterant cholestyramine. Differential effects were observed when the direct action of estradiol and progesterone on microsome preparations was examined. Cholesterol 7 alpha-hydroxylase activity was inhibited by progesterone in a dose-dependent way to almost complete abolition; similar patterns of declines were found in the three feeding groups under study. In contrast, the addition of 5 microM estradiol induced small and selective 7 alpha-hydroxylase increases in fasting and cholestryamine-fed animals, then activity declined to control values and consistent decreases were found from 20 microM. The administration of estradiol (50 micrograms) or progesterone (100 micrograms) for 21 days resulted in depressed cholesterol 7 alpha-hydroxylase activity in rats with high bile acid synthesis basal rate due to cholestyramine feeding. In rats receiving a standard diet, either ad libitum or after 24 h fasting, the hormonal effects did not reach significance. Declines in the content of free cholesterol were provoked by progesterone, not by estradiol, in liver microsomes prepared from all feeding groups. No changes in cholesterol 7 alpha-hydroxylase activity and microsomal free cholesterol were observed after administration of the sex hormones for 3 days. Rapid and transient inhibitions in 7 alpha-hydroxylase activity were found after the single injection of progesterone to fed animals. Estradiol, on the contrary, was unable to alter rapidly the hepatic 7 alpha-hydroxylase capacity.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effect of estradiol on serum cholesterol in castrated male rats Pizzichini, M., G. Cinci, et al. (1992), Biochem Soc Trans 20(4): 375S. |
| Effect of estrogen and progesterone on the hepatic cholesterol 7-alpha-hydroxylase activity in ovariectomized baboons Kushwaha, R. S. and K. M. Born (1991), Biochim Biophys Acta 1084(3): 300-2. Abstract: Cholesterol 7 alpha-hydroxylase activity was measured in livers from ovariectomized baboons fed a high cholesterol high saturated fat diet and maintained in four groups: untreated controls, estrogen (100 micrograms/g per week), progesterone (3 mg/kg per day) and estrogen + progesterone. Estrogen treatment alone increased hepatic 7 alpha-hydroxylase activity by 2.7-fold, whereas progesterone treatment alone did not influence hepatic 7 alpha-hydroxylase activity. The increase in 7 alpha-hydroxylase activity in estrogen + progesterone group was similar to that in the estrogen group. |
| Effect of ethanol on cell growth and cholesterol metabolism in cultured Hep G2 cells Polo, M. P., M. G. de Bravo, et al. (2003), Biochem Cell Biol 81(6): 379-86. Abstract: The Hep G2 human hepatoma cell line has been recognized as an excellent in vitro human model system. For this reason, this line was used to study the effect of ethanol on HMG-CoA reductase activity concerning cell growth and cholesterol metabolism. Cells were incubated in ethanol-containing medium (0-400 mmol/L) for up to 102 h. Ethanol caused an inhibition in the growth rate and in HMG-CoA reductase activity that could be reverted by the removal of ethanol from the culture medium, indicating no cellular damage. These changes cannot be ascribed to the regulatory effect of cholesterol levels, since its content was not modified either in the cells or in the medium. The addition of mevalonate to the culture medium could not revert the growth rate inhibition evoked by ethanol. Moreover, ethanol produced an increment in the cholesterol efflux in 3Hcholesterol-prelabeled cells. We conclude that the decrease in HMG-CoA reductase activity evoked by ethanol treatment on Hep G2 cells would not be the cause but the consequence of the impairment in cellular growth, since this impairment could not be reverted by the addition of mevalonate to the culture medium. |
| Effect of ethanol on cholesterol restoration in tissues of the heart and aorta Bozhko, G. and V. S. Chursina (1993), Kardiologiia 33(5): 51-5. Abstract: The time course (0.5-24 hours) of incorporation of labelled cholesterol in the tissues of guinea pig hearts, aortas, livers, and brains was examined on acute and chronic (3 months) administration of ethanol (3 g/kg). It was found that at the onset of the experiments, the hearts from control and experimental animals displayed higher radioactivity that did the other tissue under study. Within the first 24 hours, there was a linear increase in specific radioactivity of 3H-cholesterol in the sera of intact animals. Acute and chronic ethanol caused enhanced incorporation of 3H-cholesterol and its delayed release in all tissues, except the liver tissue. The latter showed unchanged relative specific radioactivity two hours after 3H-cholesterol incorporation. |
| Effect of exercise intensity and training on antioxidants and cholesterol profile in cyclists Aguilo, A., P. Tauler, et al. (2003), J Nutr Biochem 14(6): 319-25. Abstract: The aim of this work was to evaluate the effect of different intensity of exercise and different training status on antioxidants and cholesterol profile in cyclists. 33 male cyclists (17 amateur and 16 professional cyclists) participated in this study. The amateurs all trained 14 +/- 1 h each week, and their VO(2) max was 62.5 +/- 1.8 ml/Kg x min; the professionals all trained 24 +/- 1 h each week, and their VO(2) max was 80.2 +/- 1.6 ml/Kg x min. Amateurs were submitted to the maximal and submaximal prolonged exercise tests. Professionals were submitted to a mountain stage (170 km) of cycling competition. Serum lipid and cholesterol profile (triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol) and plasma antioxidant capacity (ascorbic acid, alpha-tocopherol, retinol, beta-carotene and others) were measured before and after exercise tests. Hematological determinations (number of erythrocytes, hematocrit and hemoglobin concentration) and dietary intake were also measured. No significant differences were observed in basal values (before exercise tests) of amateur and professional cyclists. Negligible differences were found between dietary intake of amateur and professional cyclists, and also the results of hematological values showed there was no effect of degree of hydration or dietary intake on blood levels of studied antioxidant and lipid parameters. An increase in plasma levels of vitamin C, vitamin E, triglycerides and VLDL-cholesterol levels, and also a decrease of beta-carotene and LDL-cholesterol. were observed in well-trained professional cyclists after the cycling stage - an endurance exercise--but not in amateur cyclists. Amateur cyclists showed only mild increases in total cholesterol after maximal and submaximal exercise, while a rise in HDL-cholesterol was only observed after maximal exercise; none of these changes were observed in professional cyclists. Plasma levels of antioxidant vitamins and carotenes, and also serum lipids, total cholesterol and lipoprotein-cholesterol showed an overall response to exercise, and their increase and/or decrease must be explained as a consequence of the different training status of sportsmen and intensity and duration of exercise tests. |
| Effect of exercise timing on postprandial lipemia and HDL cholesterol subfractions Zhang, J. Q., T. R. Thomas, et al. (1998), J Appl Physiol 85(4): 1516-22. Abstract: The purpose of the study was to examine the effect of exercise timing on postprandial lipemia responses. Subjects were 21 recreationally trained men (ages 27 +/- 1.7 yr). Each subject performed four trials: 1) Control (fat meal only), 2) Post (exercise 1 h after a fat meal), 3) 1 h-Pre (exercise 1 h before a fat meal), and 4) 12 h-Pre (exercise 12 h before a fat meal). In each trial, subjects had a standard fat meal to induce postprandial hypertriglyceridemia. Blood samples were taken at 0 h (immediately before the fat meal) and at 2, 4, 6, 8, and 24 h after the meal. In the exercise trials, each subject exercised at 60% of maximal O2 consumption for 1 h. The results indicated that triglyceride area under the curve scores in premeal-exercise trials were lower (P < 0. 05) than those in Post and Control. At 24 h, total high-density lipoprotein (HDL)-cholesterol in the premeal-exercise trials was higher (P < 0.05) than that at 0 h, whereas total HDL-cholesterol was not changed in Control and Post. At 24 h, HDL subtype 2-cholesterol was higher (P < 0.05) in the premeal-exercise trials than in Control, which did not differ from Post. These results suggest that exercising before a fat meal may have a beneficial effect on the triglyceride response and HDL metabolism, which may blunt atherosclerotic process induced by the fat meal. |
| Effect of exogenous cholesterol and dithiothreitol on the activity of human liver microsomal acyl-coenzyme A:cholesterol acyltransferase (ACAT) Smith, J. L., L. J. Madden, et al. (1996), Clin Chim Acta 256(1): 13-25. Abstract: Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is the intracellular enzyme responsible for the esterification of cholesterol with long-chain fatty acyl-CoA derivatives and has been implicated in atherosclerosis and gallstone disease. The effects of exogenous cholesterol and dithiothreitol (DTT) on the ACAT activity of human liver microsomes have been determined. Pre-incubation of microsomes with exogenous cholesterol gave a marked stimulation of activity. Experiments with 3Hcholesterol and 14Coleoyl-CoA indicated the time course of equilibration of exogenous with endogenous cholesterol as ACAT substrates, and showed that ACAT activity could be accurately measured using 3Hcholesterol/Tween 80, providing that the concentration of endogenous microsomal cholesterol was also determined. Pre-incubation of liver microsomes for 90 min in the presence of 2 mmol/l DTT and exogenous cholesterol/Tween 80 resulted in a 60% reduction in ACAT activity, compared with the corresponding activity when DTT was omitted. If microsomes were pre-incubated with DTT prior to the pre-incubation with exogenous cholesterol/Tween 80, an 85-90% reduction in ACAT activity occurred. In contrast, pre-incubation of microsomes with DTT in the absence of exogenous cholesterol/Tween 80 (only endogenous cholesterol present) resulted, initially in a stimulation of ACAT activity; on further pre-incubation, activity returned to control levels. These results indicate that the supply of cholesterol to the enzyme active site is an important factor in ACAT assays in vitro and that DTT has a major effect on this process, suggesting that these factors may be important in controlling ACAT activity in vivo. |
| Effect of exogenous hyperinsulinaemia on atherogenesis in cholesterol-fed rabbits Nordestgaard, B. G., B. Agerholm-Larsen, et al. (1997), Diabetologia 40(5): 512-20. Abstract: To examine the hypothesis that hyperinsulinaemia promotes atherosclerosis, cholesterol-fed rabbits were injected subcutaneously with 6 i.u. of human insulin (n = 16) or placebo (n = 20) daily for 24 weeks; injection of insulin resulted in hyperinsulinaemia for up to 16 h after injection. Compared to placebo rabbits, insulin-treated rabbits had higher levels of insulin antibodies in plasma, similar levels of intermediate density, low density and high density lipoprotein cholesterol and similar activities of hepatic and lipoprotein lipase in post-heparin plasma, but lower levels of plasma C-peptide, blood glucose, postprandial plasma triglycerides, plasma cholesterol and very low density lipoprotein cholesterol. On univariate analysis, with and without adjustment for differences in plasma cholesterol levels between the two groups, there were no significant differences in extent or severity of atherosclerosis between insulin and placebo rabbits. Furthermore, after combining the results from all the rabbits to examine plasma insulin levels and the other variables mentioned above as predictors of atherosclerosis severity, plasma insulin level was not a predictor, on univariate or multiple linear regression analysis; the first ranked independent predictors were postprandial intermediate density lipoprotein cholesterol in the arch, and postprandial plasma triglyceride in both the thoracic and abdominal aorta. These results suggest that exogenous hyperinsulinaemia does not promote atherogenesis in cholesterol-fed rabbits, but that postprandial levels of intermediate density lipoprotein cholesterol or plasma triglycerides may be involved in atherogenesis. |
| Effect of experimental hyper- and hypoinsulinemia on the level of cholesterol lipoproteins in aging rats Gatsko, G. G. and V. V. Gul'ko (1992), Probl Endokrinol (Mosk) 38(1): 50-2. Abstract: A study was made of the effect of hyper- and hypoinsulinemia on blood serum lipoproteins of 5-6-month and 24-26 month old rats. Total cholesterol levels, cholesterol fraction concentration in lipoproteins, the level of insulinemia, and age showed correlation. Administration of insulin had a positive effect on the serum lipid spectrum, increasing the HDL-C content in aged animals. In alloxan diabetes, VLDL-C concentration in serum was on the increase. Alterations were more pronounced in young rats. |
| Effect of experimental schistosomiasis on 14C-4-cholesterol esterification by mouse liver homogenate Soares, M. G. and S. S. Borges (1990), Braz J Med Biol Res 23(1): 7-9. Abstract: The effect of experimental schistosomiasis mansoni on cholesterol esterification by mouse liver homogenate was studied using 14C-4-cholesterol. The reaction was carried out in 0.85 ml containing 10 nCi labelled cholesterol (164 nmol as an albumin-stabilized emulsion) with 30 mg tissue homogenate in 176 mM sodium phosphate buffer, pH 7.1, containing 59 microM oleic acid, 0.3 mM CoASH and 8.8 mM ATP. In experiments with liver from infected mice (N = 22), the percentage of cholesterol esterification was 6.9 +/- 0.7%/h. This rate was 52% less than that observed in normal mice (14.4 +/- 0.6%/h, N = 21). The decrease may be due to the existence of inhibitors of the cholesterol esterifying in the infected liver, increased hydrolysis of cholesteryl esters or a decrease in the synthesis of the enzyme acyl CoA:cholesterol acyl transferase by the infected liver. |
| Effect of F-1394, a potent and selective inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), on esterification of cholesterol and basolateral secretion of cholesteryl ester in Caco-2 cells Kusunoki, J., K. Aragane, et al. (1997), Nippon Yakurigaku Zasshi 110(6): 357-65. Abstract: The present study was conducted to investigate the inhibitory effect of F-1394, a potent and selective inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), on incorporation of 14C-oleic acid into cholesteryl ester in cultured Caco-2 cells, a human intestinal cell line, and compare its effect to those of other ACAT inhibitors and hypolipidemic agents. The cholesterol esterification in Caco-2 cells was strongly inhibited by F-1394 in a concentration-dependent manner with the estimated IC50 value of 71 nM. In contrast, the estimated IC50 values of the other ACAT inhibitors such as YM-17E, CI-976, CL-277,082 and DL-melinamide are 121 nM, 702 nM, 21.5 microM and 20.9 microM, respectively. Simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, also inhibited the ACAT activity in Caco-2 cells with an IC50 value of 22.5 microM, whereas pravastatin Na, probucol and clofibrate did not affect the activity. Furthermore, F-1394 at a concentration of 100 nM inhibited the basolateral secretion of cholesteryl ester by 90% from differentiated Caco-2 cells that were cultured on a membrane filter. These results demonstrate that F-1394 strongly inhibits human intestinal ACAT activity and basolateral secretion of cholesterol from Caco-2 cells. Therefore, F-1394 may have a therapeutic potential for dietary hyperlipidemic subjects. |