| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Comparison of hypocholesterolemic activities of the bile acid sequestrants cholestyramine and colestipol hydrochloride in cholesterol fed SEA quail Day, C. E. (1990), Artery 17(5): 281-8. Abstract: The pharmacopolymer bile acid sequestrants cholestyramine and colestipol hydrochloride were mixed with a diet supplemented with 0.5% cholesterol at levels of 0.25%, 0.5%, and 1.0% for cholestyramine and 0.5% and 1.0% for colestipol and fed to young, male, SEA (Susceptible to Experimental Atherosclerosis) Japanese quail (Coturnix coturnix japonica) for a period of seven days. After treatment blood was obtained by venipuncture from non-fasted animals and analyzed for serum total cholesterol concentration. Cholestyramine significantly reduced total cholesterol concentrations at all doses in a dose dependent manner. Colestipol significantly reduced total cholesterol only at the 1.0% dose. Based on these observations, cholestyramine is significantly more potent for reducing serum cholesterol in hypercholesterolemic male SEA quail than is colestipol hydrochloride. |
| Comparison of intestinal absorption of cholesterol with different plant sterols in man Heinemann, T., G. Axtmann, et al. (1993), Eur J Clin Invest 23(12): 827-31. Abstract: Intestinal absorption of cholesterol, campesterol, campestanol, stigmasterol and sitosterol were measured in 10 healthy subjects by an intestinal perfusion technique over a 50 cm segment of the upper jejunum using sitostanol as non-absorbable marker. Cholesterol absorption was highest and averaged 33%. whereas the absorption rate of sitosterol averaged 4.2% and of stigmasterol 4.8%. Higher absorption rates were found for campesterol (9.6%). Campestanol, the 5 alpha saturated derivative of campesterol, showed the highest absorption rate (12.5%) of all plant sterols. A positive correlation between the absorption rate of cholesterol and campesterol was established. In addition, there was a negative correlation between the ratio of sitosterol to cholesterol and the mass of cholesterol absorption. These results are in agreement with previous observations in animal studies, namely, that increasing the length of the side-chain of cholesterol decreases the absorbability of the sterol. Surprisingly, campestanol, the 5 alpha saturated derivate of campesterol, was shown to have higher absorbability compared with its unsaturated compound. This finding is in contrast to previous assumptions, that hydrogenisation of the nucleus double bond of a sterol causes a decrease of absorbability, as has been demonstrated for cholesterol/cholestanol and sitosterol/sitostanol. |
| Comparison of LDL-cholesterol direct measurement with the estimate using the Friedewald formula in a sample of 10,664 patients Cordova, C. M., C. R. Schneider, et al. (2004), Arq Bras Cardiol 83(6): 482-7; 476-81. Abstract: OBJECTIVE: To compare direct measurement of LDL-cholesterol (LDL-C) determined by a homogeneous method with LDL-cholesterol estimation determined by the Friedewald formula in a large heterogeneous population. METHODS: The measurements of total cholesterol (TC) and triglycerides (TG) were performed using traditional enzymatic methods. The measurements of HDL-C and LDL-C were performed using direct methods with no precipitation, and the estimation of the LDL-C fraction was calculated using the Friedewald formula. RESULTS: On linear regression analysis, the 2 methods had extremely significant correlation coefficients (P < 0.001). However, the Friedewald formula had a positive bias in regard to the direct method, more pronounced with TC levels > 201 mg/dL. This positive bias also occurred in regard to TG levels < or =150 mg/dL. No bias was observed between the methods for TG levels ranging from 151 to 200 mg/dL and from 201 to 300 mg/dL. On the other hand, for TG levels ranging from 301 to 400 mg/dL, this bias of the Friedewald formula became negative. CONCLUSION: The Friedewald formula did not have a homogeneous performance for estimating LDL-C levels in samples with different TG levels as compared with that of the direct method, what could launch doubts on patients classification on the risk of developing coronary artery disease. |
| Comparison of LDL-cholesterol results calculated by using apolipoproteins A1, B or HDL-cholesterol for classification of non-chylomicron dyslipidemias Szmidt-Adjid, V., A. Campier, et al. (1999), Ann Biol Clin (Paris) 57(3): 345-50. |
| Comparison of levels of large and small high-density lipoprotein cholesterol in Asian Indian men compared with Caucasian men in the Framingham Offspring Study Bhalodkar, N. C., S. Blum, et al. (2004), Am J Cardiol 94(12): 1561-3. Abstract: Asian Indians have a higher incidence of coronary artery disease (CAD) than do other ethnic groups, despite similar standard risk factors and lipid profiles. The large subclass of high-density lipoprotein (HDL) cholesterol is predominantly associated with protection against coronary artery disease. We compared various lipoprotein concentrations and sizes in 211 healthy Asian Indian men with those in 1,684 Caucasian men from the Framingham Offspring Study as measured by nuclear magnetic resonance spectroscopy. Concentrations of HDL cholesterol were similar in the 2 groups, but concentrations of large HDL cholesterol were lower and concentrations of small HDL cholesterol were significantly higher in Asian Indian than in Caucasian men. HDL particle size was smaller in Asian Indians. Levels of low-density lipoprotein cholesterol, low-density lipoprotein particle size, and prevalence of pattern B were similar in the 2 groups. |
| Comparison of low-density lipoprotein cholesterol lowering by pravastatin to <100 mg/dl versus >100 mg/dl on brachial artery vasoreactivity in patients with severe hypercholesterolemia and previous atherosclerotic events or diabetes mellitus Lekakis, J. P., C. M. Papamichael, et al. (2002), Am J Cardiol 89(7): 857-60. |
| Comparison of measurements of cholesterol, glucose and uric acid taken at 5-year intervals in children and adolescents Spyckerelle, Y., J. Steinmetz, et al. (1992), Arch Fr Pediatr 49(10): 875-81. Abstract: BACKGROUND. There are several reports on cardiovascular disease risk factors but, except for lipids and lipoproteins, there have been few studies tracking blood uric acid and glucose in healthy school children. MATERIAL AND METHODS. Blood specimens were collected from 4,299 children and adolescents for determination of cholesterol, uric acid and glucose. The first samples were collected between 1977 and 1979 from subjects aged 4 to 17 years. The second samples were collected 5 years later. RESULTS. The blood glucose concentrations increased before the age of 10 years; those of uric acid increased during the second decade and those of cholesterol decreased during puberty, to a greater degree in boys. Hypercholesterolemia (cholesterol > 5.9 mmol/l) was found in about 6% of boys and 10% of girls. Eight boys and 3 girls had blood glucose concentrations higher than 6.7 mmol/l at the first collection. 5 years later, the correlation coefficients by sex and by cross section of age were greater than 0.5 for cholesterol and uric acid and were about 0.3 for glucose. CONCLUSIONS. Successive blood values of glucose and uric acid are highly correlated; those of cholesterol are more highly correlated. However, the probability of remaining in the same percentile distribution remains below 50% for subjects whose initial values were above the 80th percentile. |
| Comparison of methods for measurement of apolipoprotein B and cholesterol in low-density lipoproteins Vrga, L., C. Contacos, et al. (1997), Clin Chem 43(2): 390-3. Abstract: We describe a new method for the direct measurement of LDL-apolipoprotein (apo) B by using a commercial kit that isolates LDL by immunoseparation. We evaluated immunoseparation of LDL for apo B and cholesterol measurement in 46 dyslipidemic patients with LDL-cholesterol (LDL-C) between 1.5 and 8.2 mmol/L, 11 of whom had plasma triglyceride (TG) concentrations >4.0 mmol/L. There was a reasonable correlation (r = 0.94, n = 40) between LDL-apo B obtained after immunoseparation and d >1.006 kg/L apo B obtained after ultracentrifugation. LDL-C by the immunoseparation method also correlated well (r = 0.98, n = 46) with the d >1.006 kg/L cholesterol after ultracentrifugation. These results show that immunoseparation can be used to determine LDL-apo B, even in hypertriglyceridemic samples. This method may provide a quick and simple alternative for the identification of hyperapobetalipoproteinemia, even when TG concentrations are high. |
| Comparison of muscle fatty acid profiles and cholesterol concentrations of bison, beef cattle, elk, and chicken Rule, D. C., K. S. Broughton, et al. (2002), J Anim Sci 80(5): 1202-11. Abstract: The objective of this study was to compare fatty acid weight percentages and cholesterol concentrations of longissimus dorsi (LD), semitendinosus (ST), and supraspinatus (SS) muscles (n = 10 for each) of range bison (31 mo of age), feedlot-finished bison (18 mo of age), range beef cows (4 to 7 yr of age), feedlot steers (18 mo of age), free-ranging cow elk (3 to 5 yr of age), and chicken breast. Lipids were analyzed by capillary GLC. Total saturated fatty acids (SFA) were greater (P < 0.01) in range bison than in feedlot bison and were greater (P < 0.01) in SS of range beef cattle than in feedlot steers. Muscles of elk and range bison were similar (P > 0.05) in SAT. In LD, polyunsaturated fatty acids (PUFA) were highest (P < 0.01) for elk and range bison and lowest (P < 0.01) for feedlot steers within each muscle. Range bison and range beef cows had greater (P < 0.01) PUFA in LD and ST than feedlot bison or steers, respectively. Range-fed animals had higher (P < 0.01) n-3 fatty acids than feedlot-fed animals or chicken breast. Chicken breast n-6 fatty acids were greater (P < 0.01) than for muscles from bison, beef, or elk. Elk had higher (P < 0.01) n-6 fatty acids than bison or beef cattle; however, range-fed animals had higher (P < 0.01) n-6 fatty acids than feedlot-fed animals in ST. Conjugated linoleic acid (CLA, 18:2cis-9, trans-11) in LD was greatest (P < 0.01) for range beef cows (0.4%), and lowest for chicken breast and elk (mean = 0.1%). In ST, CLA was greatest (P < 0.01) for range and feedlot bison and range beef cows (mean = 0.4%) and lowest for elk and chicken breast (mean = 0.1%). Also, SS CLA was greatest (P < 0.01) for range beef cows (0.5%) and lowest for chicken breast (0.1%). Mean total fatty acid concentration (g/100 g tissue) for all muscles was highest (P < 0.01) for feedlot bison and feedlot cattle and lowest (P < 0.01) for range bison, range beef cows, elk, and chicken. Chicken breast cholesterol (mg/100 g tissue) was higher (P < 0.01) than LD and ST cholesterol, which were lowest (P < 0.01; 43.8) for range bison and intermediate for the other species. Cholesterol in SS was highest (P < 0.01) for feedlot bison and steers, which were similar to chicken breast (mean = 61.2 vs 52.8 for the mean of the other species). We conclude that lipid composition of bison muscle varies with feeding regimen, and range-fed bison had muscle lipid composition similar to that of forage-fed beef cows and wild elk. |
| Comparison of NCEP performance specifications for triglycerides, HDL-, and LDL-cholesterol with operating specifications based on NCEP clinical and analytical goals Fallest-Strobl, P. C., E. Olafsdottir, et al. (1997), Clin Chem 43(11): 2164-8. Abstract: The National Cholesterol Education Program (NCEP) performance specifications for methods that measure triglycerides, HDL-cholesterol, and LDL-cholesterol have been evaluated by deriving operating specifications from the NCEP analytical total error requirements and the clinical requirements for interpretation of the tests. We determined the maximum imprecision and inaccuracy that would be allowable to control routine methods with commonly used single and multirule quality-control procedures having 2 and 4 control measurements per run, and then compared these estimates with the NCEP guidelines. The NCEP imprecision specifications meet the operating imprecision necessary to assure meeting the NCEP clinical quality requirements for triglycerides and HDL-cholesterol but not for LDL-cholesterol. More importantly, the NCEP imprecision specifications are not adequate to assure meeting the NCEP analytical total error requirements for any of these three tests. Our findings indicate that the NCEP recommendations fail to adequately consider the quality-control requirements necessary to detect medically important systematic errors. |
| Comparison of plasma clearance of low density lipoprotein with beta-very low density lipoprotein or acetoacetylated low density lipoprotein in cholesterol-fed rabbits Asai, K., T. Hayashi, et al. (1991), Biochem Int 23(2): 327-34. Abstract: The plasma clearance and tissue distribution of radioiodinated low-density lipoprotein (LDL), beta-very low density lipoprotein (beta-VLDL), and acetoacetylated LDL were studied in cholesterol-fed rabbits. Radioiodinated LDL (125ILDL) was cleared more slowly than either 125Ibeta-VLDL or acetoacetylated-125ILDL and its fractional catabolic rate was one-half that of 125Ibeta-VLDL and one-ninth that of acetoacetylated-125ILDL. Forty-eight hours after the injection of the labeled lipoproteins, the hepatic uptake was the greatest among the organs evaluated with the uptake of 125ILDL being one-third that of either 125Ibeta-VLDL or acetoacetylated-125ILDL. The reduction in the hepatic uptake of LDL due to a down-regulation of the receptors would account for this retarded plasma clearance. |
| Comparison of proximate composition and fatty acid and cholesterol content of lean and typical commercial pork Bales, C. W., K. L. Moreno, et al. (1998), J Am Diet Assoc 98(11): 1328-30. |
| Comparison of regulative functions between dietary soy isoflavones aglycone and glucoside on lipid metabolism in rats fed cholesterol Kawakami, Y., W. Tsurugasaki, et al. (2005), J Nutr Biochem 16(4): 205-12. Abstract: The effects of dietary soy isoflavones aglycone and glucoside on lipid metabolism were compared in male Sprague-Dawley rats (4 weeks old) given purified diets containing 0.3% cholesterol. The rats were fed a diet supplemented with either isoflavone aglycone-rich powder (IF-A group) or isoflavone glucoside-rich powder (IF-G group) or isoflavone-free diet (control group) for 40 days. The additional level of isoflavone aglycone moiety in the diet was prepared to the same level (approximately 0.096 g/100 g: approximately 0.1% in diet). The activity of hepatic cholesterol 7alpha-hydroxylase tended to be slightly higher in the rats fed isoflavones than in those fed the isoflavone-free diet. On the other hand, the activity of hepatic Delta6 desaturase in the IF-A group was lower than that of the control group. Reflecting this effect, the Delta6 desaturation indices (20:3n-6+20:4n-6)/18:2n-6 in liver phospholipids of the IF-A group were lower than those in the control group. Liver and serum total cholesterol levels and liver TG level were also reduced by consumption of isoflavone aglycone. Moreover, serum TG level was lowered by consumption of both isoflavones aglycone and glucoside. The level of serum total isoflavones in the IF-A group was significantly higher than that in the IF-G group. Therefore, we speculate that the absorption speed of isoflavone aglycones might be faster than that of isoflavone glucosides in rats. This study suggests that dietary soy isoflavones, particularly their aglycone form, may exert a beneficial effect on lipid metabolism in rats fed cholesterol. |
| Comparison of synthetic saponin cholesterol absorption inhibitors in rabbits: evidence for a non-stoichiometric, intestinal mechanism of action Morehouse, L. A., F. W. Bangerter, et al. (1999), J Lipid Res 40(3): 464-74. Abstract: The hypocholesterolemic activities of pamaqueside and tiqueside, two structurally similar saponins, were evaluated in cholesterol-fed rabbits. The pharmacological profiles of the saponins were virtually identical: both dose-dependently decreased the intestinal absorption of labeled cholesterol 25-75%, increased fecal neutral sterol excretion up to 2.5-fold, and decreased hepatic cholesterol content 10-55%. High doses of pamaqueside (>5 mg/kg) or tiqueside (>125 mg/kg) completely prevented hypercholesterolemia. Decreases in plasma and hepatic cholesterol levels were strongly correlated with increased neutral sterol excretion. Ratios of neutral sterol excreted to pamaqueside administered were greater than 1:1 at all doses, in opposition to the formation of a stoichiometric complex previously suggested for tiqueside and other saponins. Ratios in tiqueside-treated rabbits were less than unity, a reflection of its lower potency. Pamaqueside-treated rabbits exhibited a more rapid decline in plasma cholesterol concentrations than control animals fed a cholesterol-free diet, indicating that the compound also inhibited the absorption of biliary cholesterol. Intravenous administration of pamaqueside had no effect on plasma cholesterol levels despite plasma levels twice those observed in rabbits given pamaqueside orally.These data indicate that pamaqueside and tiqueside induce hypocholesterolemia by blocking lumenal cholesterol absorption via a mechanism that apparently differs from the stoichiometric complexation of cholesterol hypothesized for other saponins. |
| Comparison of taurine, alpha-tocopherol, retinol, selenium, and total triglycerides and cholesterol concentrations in cats with cardiac disease and in healthy cats Fox, P. R., E. A. Trautwein, et al. (1993), Am J Vet Res 54(4): 563-9. Abstract: Epidemiologic relations were evaluated between plasma concentrations of nutrients and cardiovascular diseases. A total of 220 cats were assessed: 144 cats with noninduced acquired heart disease and 76 clinically normal cats. Plasma was assayed for taurine, alpha-tocopherol, selenium, retinol, and total cholesterol and triglycerides concentrations. Cardiovascular disease groups included dilated cardiomyopathy (n = 53), left ventricular hypertrophy (n = 28), hyperthyroidism (n = 11), and uncertain classification (n = 52). In cats with dilated cardiomyopathy, mean plasma taurine concentration was the lowest of that in cats of any group, being only 38% of the value in healthy cats; females had less than half the mean value of males. Tocopherol concentration was 20% lower than normal, and retinol concentration was 40% higher than normal. Total cholesterol concentration was 36% lower than normal. Triglycerides concentration was higher in these cats than in any other group--twice the value recorded in healthy cats and 67% higher than that in hyperthyroid cats. In cats with hypertrophic cardiomyopathy, almost 15% had mean plasma taurine concentration < 30 mumol/L. Retinol concentration was 15% higher, and triglycerides concentration was 54% higher than normal. Approximately 27% of hyperthyroid cats had mildly decreased plasma taurine concentration. Hyperthyroid cats had the lowest tocopherol and cholesterol values; both were at least 30% lower than normal. Retinol concentration was 30% higher than normal. Approximately 14% of cats with uncertain classification had mildly decreased plasma taurine concentration. Plasma retinol and triglycerides concentrations were higher than normal in 25 and 38% of these cats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Comparison of the activity and disposition of the novel cholesterol absorption inhibitor, SCH58235, and its glucuronide, SCH60663 van Heek, M., C. Farley, et al. (2000), Br J Pharmacol 129(8): 1748-54. Abstract: Previous studies described the metabolism-based discovery of a potent, selective inhibitor of intestinal absorption of cholesterol, SCH58235 (Ezetimibe). Here we demonstrate that the phenolic glucuronide (SCH60663) of SCH58235, was more potent at inhibiting cholesterol absorption in rats than SCH58235, when administered by the intraduodenal route. To understand the increased potency of the glucuronide, the metabolism and distribution of SCH58235 and SCH60663 were studied in bile duct-cannulated rats. One minute after intraduodenal delivery of SCH58235, significant levels of compound were detected in portal plasma; >95% was glucuronidated, indicating that the intestine was metabolizing SCH58235 to its glucuronide. When intraduodenally delivered as SCH58235, the compound was glucuronidated, moved through the intestinal wall, into portal plasma, through the liver, and into bile. However, when delivered as SCH60663, >95% of the compound remained in the intestinal lumen and wall, which may explain its increased potency. Significant inhibition of cholesterol absorption and glucuronidation of SCH58235 occurred when SCH58235 was intravenously injected into bile duct-cannulated rats. Autoradiographic analysis demonstrated that drug related material was located throughout the intestinal villi, but concentrated in the villus tip. These data indicate that (a) SCH58235 is rapidly metabolized in the intestine to its glucuronide; (b) once glucuronidated, the dose is excreted in the bile, thereby delivering drug related material back to the site of action and (c) the glucuronide is more potent than the parent possibly because it localizes to the intestine. Taken together, these data may explain the potency of SCH58235 in the rat (ID(50) = 0.0015 mg kg(-1)) and rhesus monkey (ID(50) = 0.0005 mg kg(-1)). |
| Comparison of the antiatherogenic effects of isradipine and ramipril in cholesterol-fed rabbits: I. Effect on progression of atherosclerosis and endothelial dysfunction Riezebos, J., W. Vleeming, et al. (1994), J Cardiovasc Pharmacol 23(3): 415-23. Abstract: This study was designed to compare the effects of a calcium antagonist (isradipine) and a converting enzyme inhibitor (ramipril) on progression and regression of atherosclerosis in hypercholesterolemic rabbits. Sixty rabbits in three groups were fed a 0.3% cholesterol diet for 4 weeks. After this induction period, group II received the 0.3% cholesterol diet, group III received cholesterol diet with isradipine (0.33 mg/kg/day), and group IV received cholesterol with ramipril (0.33 mg/kg/day) for 12 more weeks. A group of 20 rabbits received a standard diet throughout the study (group I). After 16 weeks, 10 rabbits were randomly chosen from each group and used in the progression study. The other rabbits were placed on a standard diet and remained on their respective drug regimen for 12 more weeks. In the progression phase of the study, ramipril significantly attenuated the percentage of aortic lesions in group IV (35 +/- 6%) as compared with group II (56 +/- 6%, p < 0.05), whereas isradipine had no effect. Acetylcholine (ACh)-induced maximum endothelium-dependent relaxations (EDR) of aortic rings were significantly reduced by the atherogenic diet to 37 +/- 4 versus 77 +/- 2% in group I (p < 0.05). Treatment with ramipril significantly improved maximum EDR to 53 +/- 3% (p < 0.05 vs. group II). Isradipine had no significant effect on impaired EDR. Aortic rings with endothelium from group II developed supersensitivity to sodium nitroprusside (SNP) and had significantly reduced basal cyclic GMP levels as compared with those of group I. Both drugs prevented development of supersensitivity to SNP and blunted the cholesterol-induced reduction in basal cyclic GMP levels.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Comparison of the antiatherogenic effects of isradipine and ramipril in cholesterol-fed rabbits: II. Effect on regression of atherosclerosis and restoration of endothelial function Riezebos, J., W. Vleeming, et al. (1994), J Cardiovasc Pharmacol 23(3): 424-31. Abstract: We report the effects of isradipine and ramipril on regression of diet-induced atherosclerosis in rabbits. Regression of diet-induced atherosclerosis was not significantly affected by ramipril, but isradipine significantly retarded regression. Thirty rabbits in three groups were fed a 0.3% cholesterol diet for 4 weeks. After this induction period, group IIr received the 0.3% cholesterol diet, group IIIr received the 0.3% cholesterol diet with isradipine (0.33 mg/kg/day), and group IVr received the 0.3% cholesterol diet with ramipril (0.33 mg/kg/day) for 12 more weeks. The rabbits then received a standard diet and remained on their respective drug regimen for 12 more weeks. Group Ir (10 rabbits) received a standard diet for 28 weeks. Acetylcholine (ACh)-induced maximal endothelium-dependent relaxations (EDR) of aortic rings were significantly less in group IIr (22.8 +/- 3.2%) than in group Ir (66.4 +/- 4.0%; p < 0.05). Ramipril and isradipine did not improve EDR as compared with group IIr. Regression of atherosclerosis was accompanied by an improved endothelium-dependent releasing factor (EDRF) release from the endothelium, but ramipril and isradipine did not promote this process. In addition, regression was associated with increasing sensitivity of vascular smooth muscle to EDRF that was significantly retarded by isradipine but not ramipril. Basal cyclic GMP levels were significantly reduced in aortic rings from group IIr as compared with group Ir. Ramipril, but not isradipine, restored basal cyclic GMP levels to control values. Both isradipine and ramipril protect against endothelial degeneration in hypercholesterolemic rabbits. However, isradipine but not ramipril inhibits regression of diet-induced atherosclerosis in rabbits. |
| Comparison of the antiatherosclerotic effect of tibolone with that of estradiol and ethinyl estradiol in cholesterol-fed, ovariectomized rabbits Zandberg, P., J. L. M. Peters, et al. (2001), Menopause 8(2): 96-105. Abstract: OBJECTIVE: Tibolone is a synthetic steroid with tissue-specific estrogenic, progestogenic, and androgenic properties. The drug relieves climacteric symptoms and prevents osteoporosis but does not stimulate the endometrium. We have previously shown that in laboratory animals tibolone inhibits the atherogenesis induced by a high-cholesterol diet. Therefore, we compared the antiatherosclerotic effect of oral tibolone at different dose levels with that of oral 17beta-estradiol (E2) and ethinyl estradiol (EE). DESIGN: Atherosclerotic lesion formation (increase in vessel wall cholesterol deposition and fatty streak formation) was measured in ovariectomized rabbits after 20 weeks on an atherogenic diet (fed daily 80 g of a rabbit chow containing 0.4% cholesterol, 3.75% peanut oil, and 3.75% coconut oil) in eight groups: group 1, placebo (n = 35); group 2, control (n = 34) received normal rabbit chow; group 3, E2 group (E2 4 mg, n = 12); group 4, EE group (EE 60 microg, n = 10); and groups 5-8, tibolone (6 mg, n = 12; 2 mg, n = 13; 0.6 mg, n = 25; and 0.15 mg, n = 11, respectively). During the study, blood samples were obtained for the evaluation of plasma triglycerides, cholesterol, lipoproteins, and glutamate pyruvate transaminase. After 20 weeks, the animals were killed, and cholesterol concentration and the formation of fatty streaks in the wall of the aortic arch were evaluated. RESULTS: In the placebo group, the atherogenic diet induced a mean increase in total plasma cholesterol concentration from 1.1+/-0.1 mmol/L (control group) to 34.1+/-1.8 mmol/L (mean +/- SE). This resulted in an accumulation of cholesterol in the aortic arch from 48+/-4 (control group) to 608+/-44 nmol/mg protein and in the formation of fatty streaks (41.8+/-3.2% of the surface of the aortic arch was covered with fatty streaks). Tibolone had strong dose-dependent antiatherosclerotic effects. It reduced the accumulation of cholesterol in the aortic arch at doses of 6 to 0.15 mg by 99, 97, 87, and 57% and the formation of fatty streaks by 98, 97, 81, and 38%, respectively. E2 had only a marginal antiatherosclerotic effect, whereas EE showed an effect comparable to that of tibolone at doses of 2 to 0.6 mg. With EE, the accumulation of cholesterol in the vessel wall was reduced by 93% and the formation of fatty streaks by 73%. Mean plasma cholesterol concentrations were also reduced by tibolone (64, 70, 61, and 47%) and EE (57%). This reduction was mainly mediated via a reduction in beta-very-low-density lipoprotein cholesterol. Analysis, however, indicated that the observed antiatherosclerotic effects of tibolone and EE, at least partly, are due to a direct effect on the vessel wall and independent of the changes in plasma cholesterol. At equipotent antiatherosclerotic doses, EE showed a stronger uterotropic effect (measured as the increase in uterine weight) than tibolone. EE increased uterine weight from 0.57 g/kg body weight (BW) (control group) to 3.5 g/kg BW; tibolone at doses of 6, 2, 0.6, and 0.15 mg increased uterine weight to 2.5, 2.8, 2.2, and 1.3 g/kg BW, respectively. CONCLUSION: Tibolone can protect the arterial vessel wall against atherosclerotic lesions induced by a hypercholesterolemic diet. However, it has much less estrogenic effects on the uterus compared with EE at equipotent doses, indicating tissue selectivity for tibolone. The clinical implications of these findings require investigation. |
| Comparison of the apoptotic processes induced by the oxysterols 7beta-hydroxycholesterol and cholesterol-5beta,6beta-epoxide Ryan, L., Y. C. O'Callaghan, et al. (2004), Cell Biol Toxicol 20(5): 313-23. Abstract: Oxysterols have been shown to induce apoptosis in a variety of cell lines. The mechanism of oxysterol-induced apoptosis is mainly known at the post-mitochondrial level. The aim of the present study was to compare the pathway of apoptosis induced by the oxysterols 7beta-hydroxycholesterol (7beta-OH) and cholesterol-5beta,6beta-epoxide (beta-epoxide) in U937 cells. To this end, we employed a range of inhibitors of apoptosis; a broad-spectrum caspase inhibitor, a specific caspase-3 inhibitor and an inhibitor of cytochrome c release and the antioxidants; trolox, ebselen and resveratrol. The three inhibitors of apoptosis prevented cell death induced by 7beta-OH; however, in beta-epoxide-treated cells, the inhibitor of cytochrome c release did not protect against apoptosis. The cellular antioxidant glutathione was depleted in 7beta-OH-treated cells but not in cells incubated with beta-epoxide. Trolox, a water-soluble synthetic analogue of alpha-tocopherol, prevented 7beta-OH-induced apoptosis but did not protect against cell death induced by beta-epoxide. Ebselen and resveratrol did not protect U937 cells against apoptosis induced by either 7beta-OH or beta-epoxide. Our results suggest that differences occur in the pathways of apoptosis induced by 7beta-OH and beta-epoxide in U937 cells. |