| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
| First Page | Previous Page | Next Page | Last Page |
| Antiatherosclerotic agents. A structurally novel bivalent inhibitor of acylCoA:cholesterol O-acyltransferase with systemic activity Gammill, R. B., F. P. Bell, et al. (1990), J Med Chem 33(10): 2685-7. |
| Anti-atherosclerotic and plasma lipid lowering effects of the novel calcium blocker with alpha 1-adrenoceptor antagonistic activity, monatepil, in high cholesterol diet-fed Japanese Macaca fuscata monkeys Miyazaki, M., K. Hosoki, et al. (1994), Arzneimittelforschung 44(3): 288-97. Abstract: 1. The preventive effects of atherosclerosis and hyperlipidemia of monatepil ((+-)-N-(6,11-dihydrodibenzo b,ethiepin-11-yl)-4-(4-fluorophenyl)-1-piperazine-butanamide+ + +monomaleate, AJ-2615, CAS 103377-41-9), a new antihypertensive drug with potent calcium antagonistic and alpha 1-adrenoceptor blocking activities, were investigated in Japanese monkeys (Macaca fuscata) fed with a cholesterol-rich diet (2% cholesterol + 6% corn oil) and compared with those of prazosin. 2. The dose of monatepil selected (30 mg/kg/d, p.o., 6 months) was the plasma concentration dose level of antihypertensive therapy and that of prazosin (2 mg/kg twice daily, p.o., 6 months) was the dose where hypolipidemic effect in cholesterol-fed monkeys has been reported. 3. In the cholesterol diet control group (n = 7), plasma levels of total cholesterol and low-density lipoprotein (LDL) significantly increased and that of high-density lipoprotein-cholesterol (HDL-C) decreased compared with the normal diet group (n = 5). In the monatepil group (n = 5), these changes were significantly suppressed. In the prazosin group (n = 5), these changes were also inhibited but the inhibitory effect was weaker than in the monatepil group. 4. The cholesterol content and sudanophilic area in the aorta indicating atheromatous lesions in the cholesterol-diet fed control group were significantly higher than those in the normal diet control group. In the monatepil group, these changes were significantly suppressed whereas in the prazosin group these changes were partially inhibited. 5. In the histological study, aortic lesions characterized by aggregations of foam cells were observed in the cholesterol-diet control group, while there was little change in the monatepil group. The anti-atherogenic effect of prazosin was weaker than that of monatepil. 6. Coronary atheromatous lesions were found in 4 out of the 7 animals in the cholesterol-diet control group and 3 out of the 5 animals in prazosin group. In contrast, no coronary atheromatous lesion was found in the monatepil group. 7. The treatment with monatepil did not influence food consumption, body weight, physical signs or blood biochemistry. 8. The anti-atherosclerotic and plasma lipid-lowering effects of monatepil may in part be attributable to its calcium antagonistic, alpha 1-adrenoceptor blocking, and anti-lipid peroxidation activities. 9. In conclusion, monatepil is a new class of antihypertensive agent that possesses anti-atherogenic properties and the ability to reduce plasma lipid levels, a main risk factor for atherosclerosis. |
| Antiatherosclerotic effect of alacepril, an angiotensin-converting enzyme inhibitor, in monkeys fed a high-cholesterol diet Miyazaki, M. and S. Takai (1999), Hypertens Res 22(1): 49-54. Abstract: We investigated the effects of 6 months' treatment with the angiotensin-converting enzyme (ACE) inhibitor alacepril, given in low (100 mg/kg/d, p.o.) and high (200 mg/kg/d, p.o.) doses, on the development of atherosclerotic lesions in the aorta of monkeys fed a high-cholesterol diet for 6 mo. Mean blood pressures in the normal-diet group, high-cholesterol-diet group, and high-cholesterol-diet group treated with a low dose of alacepril were very similar, while that in the high-cholesterol-diet group treated with a high dose of alacepril was significantly reduced. The level of low-density lipoprotein in the high-cholesterol-diet group was significantly higher than that in the normal-diet group, and the levels in the alacepril groups were significantly lower than those in the high-cholesterol-diet group. Atherosclerotic lesions in the normal- and high-cholesterol-diet groups were 13.2 +/- 0.34% and 64.1 +/- 10.48%, respectively, and those in the groups treated with low and high doses of alacepril were 32.3 +/- 13.2% and 16.0 +/- 1.57%, respectively. Angiotensin-converting enzyme (ACE) activity in the thoracic aorta in the high-cholesterol-diet group was significantly higher than that in the normal-diet group, and the ACE activities in the alacepril groups were lower than that in the high-cholesterol-diet group. We conclude that alacepril prevents the development of atherosclerosis by reducing vascular ACE activity in monkeys given a high-cholesterol diet. |
| Anti-atherosclerotic effect of E5324, an inhibitor of acyl-CoA:cholesterol acyltransferase, in Watanabe heritable hyperlipidemic rabbits Kogushi, M., H. Tanaka, et al. (1996), Atherosclerosis 124(2): 203-10. Abstract: E5324, n-butyl-N'-2-3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy-6- methylphenylurea, a novel and potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), was evaluated for its anti-atherosclerotic and lipid-lowering effects in Watanabe heritable hyperlipidemic (WHHL) rabbits. At 3 months of age, 40 male WHHL rabbits were divided into 4 groups. The rabbits were fed a standard rabbit chow (control group), or standard rabbit chow containing E5324 (0.1% or 0.02%) or 1% probucol for 16 weeks. Even the high dose of E5324 did not lower the plasma total cholesterol levels throughout the experiment. Probucol slightly reduced the plasma cholesterol levels, and showed anti-atherosclerotic activity, i.e., reductions of atherosclerotic plaque formation and cholesterol content in the aorta. Although E5324 did not lower plasma cholesterol, atherosclerotic plaque formation in the aortic arch and thoracic aorta was reduced (by about 34% and 41%, respectively, at the high dose; P < 0.05). Cholesterol content in the aortic arch and thoracic aorta was also reduced (by about 59% and 62% at the high dose, respectively) compared with the control. These results suggest that E5324 acts directly on the arterial wall through ACAT inhibition, and prevents the progression of atherosclerosis in WHHL rabbits. |
| Antiatherosclerotic effect of Lipotab Forte in cholesterol-fed rabbits Raj kumar, S., K. K. Pillai, et al. (1998), J Ethnopharmacol 59(3): 125-30. Abstract: The effect of Lipotab Forte, a new polypharmaceutical herbal formulation developed on the principles of the Unani system of medicine, was investigated on the progression of atherosclerosis in cholesterol fed rabbits. Retardation of the progression of atherosclerosis was observed in animals treated with Lipotah Forte. The results were related to changes in the cholesterol content of aorta from the same animal. Blood cholesterol and triglyceride levels were greatly elevated in all rabbits on cholesterol feeding, but were significantly decreased by Lipotab Forte treatment. Lipotab Forte treatment also lowered aorta Thiobarbituric acid reactive substance (TBARS) levels from 79.72 (+/-5.70) to 24.9 (+/-2.04) nmol/g of wet tissue and reduced hepatic cholesterol significantly in hypercholesterolemic rabbits. |
| Anti-atherosclerotic effects of an angiotensin converting enzyme inhibitor and an angiotensin II antagonist in Cynomolgus monkeys fed a high-cholesterol diet Miyazaki, M., H. Sakonjo, et al. (1999), Br J Pharmacol 128(3): 523-9. Abstract: 1. We investigated the relationship between angiotensin II formation and the development of atherosclerotic lesions in the aorta of monkeys (Macaca fascicularis) fed a high-cholesterol (4% cholesterol and 6% corn oil) diet for 6 months, and studied the effects of an angiotensin converting enzyme (ACE) inhibitor, trandolapril (10 mg kg-1 per day, p.o.), and an angiotensin II type 1 receptor antagonist, 2-butyl-4-(methylthio)-1-2'(propylamino)carbonylaminosulfonyl (1,1'-biphenyl)-4-ylmethyl-1H-imidazole-5-carboxylate (HR 720; 20 mg kg-1 per day, p.o.). 2. The level of low-density lipoprotein was significantly increased by the cholesterol diet, whereas that of high-density lipoprotein was significantly decreased. The relative areas of the atherosclerotic lesions in the thoracic aorta in the normal and cholesterol-diet groups were 1.3+/-0.3 and 64+/-10%, respectively. 3. Plasma renin and ACE activities showed no differences between the normal and cholesterol-diet groups. ACE activity and the concentration of angiotensin II were significantly increased in the aorta of the cholesterol-fed monkeys. 4. Trandolapril and HR 720 decreased significantly the area of the atherosclerotic lesions in the thoracic aorta of cholesterol-fed monkeys, but not the mean blood pressure and the levels of low-density and high-density lipoproteins. 5. In plasma and aorta, trandolapril, but not HR 720, decreased significantly the ACE activities in the cholesterol-fed monkeys, while both of these drugs decreased significantly the angiotensin II levels. 6. In conclusion, blockade of angiotensin II function in vascular tissues by trandolapril or HR 720 may play an important role in preventing the development of atherosclerotic lesions. |
| Antiatherosclerotic effects of oral naftidrofuryl in cholesterol-fed rabbits involve inhibition of neutrophil function Kienbaum, P., M. Braun, et al. (1995), J Cardiovasc Pharmacol 25(5): 774-81. Abstract: We investigated the action of oral naftidrofuryl, a serotonin (5-HT2)antagonist, on atheromatous plaque formation, endothelial function, and neutrophil activity in cholesterol-fed (1% for 12 weeks) rabbits. Cholesterol feeding caused almost complete (84 +/- 4%) coverage of the aortic surface with atheromas and a marked intimal thickening. The endothelium-dependent relaxation to acetylcholine (ACh 1 nM-10 microM) and substance P (30 nM) was considerably reduced, whereas the relaxing effect to the endothelium-independent nitric oxide donor linsidomine (SIN-1) (100 microM) was unchanged. Treatment of hypercholesterolemic rabbits with naftidrofuryl (50 mg/kg body weight) resulted in a marked (54 +/- 6%, p < 0.05) reduction in aortic plaque formation. Endothelium-dependent relaxation to ACh was significantly improved in rings of both thoracic aorta: 33 +/- 5 versus 14 +/- 5% (p < 0.05) and abdominal aorta 68 +/- 9 versus 37 +/- 10% (p < 0.05). Similar results were obtained with substance P, but the responses to SIN-1 were unchanged. Zymosan-induced, luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMN) was markedly stimulated in cholesterol-fed rabbits. Naftidrofuryl reduced this hyperreactivity to that of control rabbits. There was no change by naftidrofuryl in any of these parameters in control rabbits, precluding a direct action of the compound in nonhypercholesterolemic conditions. These data demonstrate significant endothelium-protective actions of long-term oral naftidrofuryl in cholesterol-fed rabbits that involve inhibition of cholesterol-induced neutrophil activation. |
| Anti-atherosclerotic effects of tamoxifen in cholesterol-fed ovariectomized rabbits Sugama, D., H. Nakajima, et al. (2002), Jpn Heart J 43(5): 545-58. Abstract: It has been indicated that the anti-estrogen agent, tamoxifen, developed for the treatment of breast cancer, may act on the vascular system as an estrogen agonist. However, to our knowledge few reports suggest that tamoxifen exerts anti-atherogenic actions. In the present study, we evaluated the anti-atherosclerotic effects of tamoxifen in ovariectomized cholesterol-fed rabbits. Ovariectomized rabbits were fed a 1% cholesterol diet and divided into 4 groups: control group (C, n=5); estrogen treatment (E, n=6); low-dose tamoxifen treatment (0.5 mg/kg) (LT, n=6); and high-dose tamoxifen (1.0 mg/kg) (HT, n=7). After 6 weeks, both Oil red O-positive areas on the intimal surfaces of aortae and the ratios of intimal to medial areas (I/M ratios) measured from cross-sections of aortae were significantly lower in groups E, LT and HT compared with group C. Although there were no significant differences in serum NOx (NO2 and NO3) levels among the 4 groups, NOx levels were slightly higher in groups E, LT and HT than group C. Acetylcholine (ACh) was administered to all animals, and the responses of ear arteriole diameters were compared among the 4 groups. While ear arteriole diameters were significantly decreased in group C, no significant changes were observed in groups E, LT or HT following ACh administration. Ratios of ear arteriole diameters after to before ACh administration were significantly greater in groups E, LT and HT compared to group C. These findings suggest that tamoxifen exerts anti-atherosclerotic effects, and that these effects are attributed to the maintenance of vascular endothelial function. |
| Anti-atherosclerotic properties of the acyl-coenzyme A:cholesterol acyltransferase inhibitor F 12511 in casein-fed New Zealand rabbits Rival, Y., D. Junquero, et al. (2002), J Cardiovasc Pharmacol 39(2): 181-91. Abstract: SUMMARY: The anti-atherosclerotic properties of F 12511, a novel acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, were studied in rabbits that were fed a cholesterol-free casein-rich diet and developed endogenous hypercholesterolemia and fibrofatty preatheroma lesions. After 6 weeks of casein feeding, an endothelial abrasion was performed in the abdominal aorta; at week 8, a control group was maintained on this diet while F 12511 (8 mg/kg/d) was administered as a diet admixture for the subsequent 24 weeks. Total plasma cholesterol level rose to 250-300 mg/dl in both groups before starting the treatment; F 12511 time-dependently reduced total plasma cholesterol by 50%, and also decreased by 50% the incidence of lesions and macrophage accumulation in uninjured aorta (thoracic arch, celiac bifurcation). Residual lesions in the treated group were characterized by few macrophages, essentially under the endothelium, and by a larger content of smooth muscle cells. Quantitative image analysis of serial sections of mechanically injured abdominal aorta revealed a 20% surface covered by preatheroma lesions in the placebo group; F 12511 significantly reduced this surface. These data suggest that the combination of endogenous hypercholesterolemia with endothelial injury in the rabbit may offer a useful model to study atherosclerosis; lipid lowering by F 12511 reduces the incidence of vascular lesions and macrophage infiltration and may reinforce the fibrous skeleton of the atheroma. |
| Antibodies against heat shock proteins and cholesterol in HIV infection Fust, G., Z. Beck, et al. (2005), Mol Immunol 42(1): 79-85. Abstract: This review summarizes data on the presence and function of different heat shock proteins (Hsp) in the HIV virions and the infected cells. A 60 kD heat shock protein-like molecule is present in the envelope of the human immunodeficiency virus type 1 which can specifically interact with the transmembrane glycoprotein gp41. The role of cholesterol in the so-called cholesterol-rich lipid raft where HIV is budding from the infected cells as well as the consequential insertion of cholesterol into the envelope of HIV virion are also discussed. Natural antibodies against 60 kD (Hsp60) and 70 kD (Hsp70) families of Hsp and cholesterol can be detected in most healthy individuals. HIV infection results in a sharp increase in the serum concentration of anti-Hsp70 and cholesterol antibodies whereas no difference in the concentration of anti-Hsp60 antibodies can be detected. Highly active antiretroviral therapy leads to normalization of the levels of both anti-Hsp70 and anti-cholesterol antibodies. |
| Antibodies against high-density lipoprotein binding proteins enhance high-density lipoprotein uptake but do not affect cholesterol efflux from rat hepatoma cells Sviridov, D., T. Sasahara, et al. (1997), Int J Biochem Cell Biol 29(4): 583-8. Abstract: High-density lipoprotein plays a key role in the reverse cholesterol transport pathway as well as in the delivery of cholesterol to the liver and steroidogenic tissues. Metabolism of high-density lipoprotein is determined by one of its apolipoproteins, apolipoprotein A-I; however, the identity and function of cellular protein which binds high-density lipoprotein remains unclear. The effect of antibodies against rat high-density lipoprotein binding proteins, HB1 and HB2, on high-density lipoprotein metabolism in a rat hepatoma cell line were studied. Cells were preincubated with the antibodies and 125I-labeled high-density lipoprotein binding and uptake as well as cholesterol biosynthesis and cholesterol efflux to human plasma or isolated high-density lipoprotein were studied. Both antibodies reacted specifically with HB1 and HB2 on the ligand and Western blots, but their binding was not blocked by high-density lipoprotein. Both antibodies inhibited 125I-labeled high-density lipoprotein binding to cells by 20-40%, but stimulated 125I-labeled high-density lipoprotein uptake by up to 2.5-fold. The antibodies had no effect on cholesterol efflux or on cholesterol synthesis. It is concluded that high-density lipoprotein binding proteins, HB1 and HB2, may be involved in high-density lipoprotein uptake in the liver rather than in mediating cholesterol efflux. |
| Antibodies to cholesterol, cholesterol conjugates and liposomes: implications for atherosclerosis and autoimmunity Alving, C. R. and G. M. Swartz, Jr. (1991), Crit Rev Immunol 10(5): 441-53. Abstract: Polyclonal and monoclonal antibodies to cholesterol are readily induced by injecting cholesterol-loaded liposomes containing lipid A as an adjuvant. Analysis of the literature reveals that conjugates of cholesterol, and conjugates of analogues of cholesterol, with heterologous proteins or lipids have been used as antigens in various studies since 1925, and this has led to successful development of immunoassays for steroid hormones. It is concluded that cholesterol is a highly immunogenic molecule. The ability of monoclonal antibodies to cholesterol to react with liposomes containing cholesterol to cause complement-dependent immune damage to the liposomes is strongly influenced by the lipid composition of the liposomes, the amount of cholesterol in the liposomes, and the reaction temperature. The antibodies also react with crystalline cholesterol in a solid-phase ELISA and, depending on the particular monoclonal antibody, immune reactivity may or may not be observed with cholesterol esters, cholesterol analogues, or steroid hormones. Analysis by ELISA has revealed that virtually all normal human sera contain varying levels of naturally occurring IgG and IgM autoantibodies to cholesterol. Naturally occurring autoantibodies to cholesterol are also observed in pigs, but not in guinea pigs. Possible implications of these investigations for theories of immune mechanisms that may have beneficial or detrimental roles in processes of aging, atherosclerosis, and vascular diseases are discussed. |
| Antibodies to cholesterol: biological implications of antibodies to lipids Alving, C. R., N. M. Wassef, et al. (1996), Curr Top Microbiol Immunol 210: 181-6. Abstract: Injection of silicone gel or silicone oil intraperitoneally into BALB/c mice induced the formation of antibodies that reacted by ELISA with highly purified crystalline cholesterol and, to a much lesser extent, antibodies that reacted with a phospholipid (dimyristoyl phosphatidylglycerol). Although IgM and IgG antibodies to cholesterol were detected, the titers of IgG antibodies were low when compared with IgM. The titers of IgM antibodies to cholesterol in certain sera exhibited activities that reached baseline values at dilutions as high as 1:5000, thus making them equivalent to titers that have been previously published for ascites fluid containing murine monoclonal antibodies to cholesterol. The antibodies to cholesterol induced by silicone compounds are indistinguishable in their binding to crystalline cholesterol from naturally-occurring antibodies to cholesterol in normal human serum. They are also indistinguishable from antibodies induced by a proposed vaccine to cholesterol that is currently in late preclinical development for prevention of hypercholesterolemia in humans. The anti-cholesterol vaccine, which consists of liposomes heavily laden with cholesterol as an antigen and lipid A as an adjuvant, induces antibodies that react with low density lipoproteins (LDL) and opsonize them for removal by liver macrophages. It appears that silicone gel or silicone oil causes recruitment and adsorption of cholesterol at the injection site, and also serves as an adjuvant that may have immunostimulant properties similar to lipid A for inducing antibodies to lipids. Antibodies to lipids such as cholesterol or phospholipids are not harmful to intact cell membranes because of steric hindrance from surrounding lipids and larger macromolecules that block binding of the antibodies. |
| Antibodies to liposomes, phospholipids, and cholesterol: implications for autoimmunity, atherosclerosis, and aging Alving, C. R. (1990), Prog Clin Biol Res 343: 41-51. |
| Antibody titer against malondialdehyde-modified LDL compares with HDL cholesterol concentration in identifying angiographically verified coronary artery disease. Comparison of tests by ROC analysis Rontu, R., S. Metso, et al. (2005), Clin Chem Lab Med 43(4): 357-60. Abstract: Antibody titer against malondialdehyde (MDA)-modified low-density lipoprotein (LDL) has been found to be associated with atherosclerosis, but it has not been established whether it would detect subjects with coronary artery disease (CAD). In the present study, receiver-operating characteristic (ROC) analysis was used to compare the diagnostic accuracy of the antibody titer against MDA-modified LDL and high-density lipoprotein (HDL) and LDL cholesterol levels in discrimination between subjects with (n = 51) and without (n = 35) angiographically verified 3-vessel CAD. As a result, the antibody titer against MDA-modified LDL was lower in subjects with CAD compared with subjects without CAD (p < 0.0001). The area under the ROC plot was 0.822 (95% CI, 0.727 to 0.918) for the antibody titer and 0.769 (95% CI, 0.661 to 0.876) for the HDL cholesterol concentration. Both the antibody titer and the plasma HDL cholesterol level were more accurate markers of CAD than the LDL cholesterol level. As a conclusion, our results indicate that the antibody titer against MDA-modified LDL discriminates between subjects with widespread CAD and those without CAD similarly as the HDL cholesterol concentration. Moreover, the antibody titer against MDA-modified LDL is inversely correlated with the risk of severe CAD. |
| Anti-cholesterol antibodies (ACHA) in patients with different atherosclerotic vascular diseases and healthy individuals. Characterization of human ACHA Horvath, A., G. Fust, et al. (2001), Atherosclerosis 156(1): 185-92. Abstract: In animal experiments the protective role of anti-cholesterol antibodies (ACHA) in the development of atherosclerosis has been demonstrated. Despite the fact that ACHA are present in the serum of healthy humans, no data on the occurrence of these antibodies in human diseases are available. We determined serum concentrations of IgG type ACHA by an enzyme immunosorbent assay in 600 patients with atherosclerotic vascular diseases (86 patients with peripheral occlusive atherosclerosis, 146 patients with cerebrovascular diseases, 341 patients with severe coronary heart disease (CHD) who received aorto-coronary by-pass, 27 patients with myocardial infarction who did not undergo by-pass operation), in 57 patient controls (complaints of CHD, without coronarographic alterations) and in 218 healthy individuals. ACHA were present in the sera of all persons tested. No serum cofactor is needed for the binding of human ACHA to solid phase cholesterol, binding can be inhibited dose-dependently by LDL and even more strongly with LDL/VLDL preparations purified from human serum. ACHA levels were found to be considerably lower in patients with peripheral occlusive atherosclerosis and cerebrovascular diseases compared with the levels in healthy individuals. By contrast, the ACHA levels of patients with CHD were considerably higher. No differences in the IgG subclass distribution and binding efficiency of ACHA in the sera of CHD patients and controls were found. Thus, our present findings indicate that both low and high ACHA production may be associated with different atherosclerotic vascular diseases. |
| Anti-cholesterol antibodies in human sera Horvath, A. and A. Biro (2003), Autoimmun Rev 2(5): 272-7. Abstract: In the last 30 years many research showed that high serum cholesterol level is a great risk for the atherosclerosis. In recent years, it has become clear that the immune system has a major role in atherosclerosis development and progression, and has binding capacity to cholesterol as well. It has been demonstrated in animal experiments, that anti-cholesterol antibodies (ACHA) can prevent cholesterol diet induced atherosclerosis. Our group is looking for the answer, whether ACHA have the same function in animals and in humans, or not. In this review we summarize our studies in human sera. We measured serum ACHA levels in different groups of patients with atherosclerotic diseases in patients with viral infections and in healthy population. In the summary we write about the possible functions of ACHA in the human immune system. |
| Antiestrogens and the reduction in circulating cholesterol Jordan, V. C. (1996), J Clin Oncol 14(8): 2407-8. |
| Antihypercholesterolemic action of taurine on streptozotocin-diabetic rats or on rats fed a high cholesterol diet Nanami, K., H. Oda, et al. (1996), Adv Exp Med Biol 403: 561-8. |
| Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterol-regulating enzymes, fecal sterol and tissue morphology in rabbits Jeon, S. M., Y. B. Park, et al. (2004), Clin Nutr 23(5): 1025-34. Abstract: BACKGROUND & AIMS: Hyperlipidemia is a major risk factor for cardiovascular diseases. This study was designed to confirm the hypocholesterolemic role of naringin. METHODS: Male rabbits were fed 0.5% high-cholesterol diet or high-cholesterol diet supplemented with either 0.05% naringin or 0.03% lovastatin for 8 weeks. RESULTS: The naringin and lovastatin supplements significantly lowered plasma total- and LDL-cholesterol and hepatic lipids levels, while significantly increasing HDL-C/total-C ratio compared to the control group. Hepatic 3-hydroxy-3-methylglutaryl CoA reductase and acyl-CoA: cholesterol acyltransferase activities were significantly higher and lower, respectively, in both supplemented groups than the control group. Total fecal sterol content was significantly increased in lovastatin and especially naringin group. In histopathological analyses, only control group exhibited hepatic lipid droplets, cardiac adipocyte infiltration and slight damage of endothelial lining in aortic wall, but two supplements retarded these atherogenic signs. CONCLUSION: It would appear that both naringin and lovastatin contributed to hypocholesterolemic action via down-regulated ACAT activity and higher excretion of fecal sterols in response to high-cholesterol feeding. Also, naringin supplement seemed to preserve tissue morphology from damages induced by high cholesterol diet. |