Improving effect of dietary taurine supplementation on the oxidative stress and lipid levels in the plasma,liver and aorta of rabbits fed on a high-cholesterol diet

The effect of a high-cholesterol diet with or without taurine on lipids and oxidative stress in the plasma, liver and aorta of rabbits was investigated. The animals were maintained on a basal diet (control), a high-cholesterol diet (HC, 1% w/w), or a high- cholesterol diet supplemented with taurine (HCHT, 2.5% w/w) for two months. Taurine has an ameliorating effect on atherosclerosis together with a decreasing effect on the cholesterol and triglyceride levels in rabbits fed on an HC diet. The HCHT diet caused a significant decrease in the malondialdehyde (MDA) and diene conjugate (DC) levels in the plasma, liver and aorta of rabbits as compared to the HC group. This treatment did not alter the antioxidant system in the liver of rabbits in the HC group. Our findings indicate that taurine ameliorated oxidative stress and cholesterol accumulation in the aorta of rabbits fed on the HC diet and that this effect may be related to its antioxidative potential as well as its reducing effect on serum lipids.     

Effects of added dietary taurine on erythrocyte lipids and oxidative stress in rabbits fed a high cholesterol diet

Lipid peroxidation leads to damage of polyunsaturated fatty acids of membrane phospholipids. The contribution of oxidative stress to hypercholesterolemia-induced hemolytic anemia and the effects of addition of taurine on erythrocyte lipid composition, oxidative stress, and hematological data were studied in rabbits fed on a high cholesterol (HC) diet (1%, w/w) for 2 months. The effects of taurine on erythrocyte hemolysis and H2O2-induced lipid peroxidation were investigated in normal rabbit erythrocytes in vitro. The HC diet resulted in increases in plasma lipids and lipid peroxide levels as well as increases in cholesterol levels and the cholesterol:phospholipid ratio in the erythrocytes. This diet caused a hemolytic anemia, but lipid peroxide levels remained unchanged in the erythrocytes of the rabbits. Taurine (2.5%, w/w) added to the food has an ameliorating effect on plasma lipids and lipid peroxide levels in rabbits fed on a HC diet. This treatment also caused decreases in elevated erythrocyte cholesterol levels and cholesterol:phospholipid ratio due to the HC diet, but it did not prevent the hemolytic anemia and did not change erythrocyte lipid peroxide levels. In addition, in an in vitro study, taurine did not protect erythrocytes against H2O2-induced hemolysis or lipid peroxidation. These results show that the HC diet causes hemolytic anemia without any changes in erythrocyte lipid peroxidation, and taurine treatment was not effective against hemolytic anemia caused by the HC diet.     

Hazelnut oil administration reduces aortic cholesterol accumulation and lipid peroxides in the plasma, liver, and aorta of rabbits fed a high-cholesterol diet

Hazelnut oil (HO) is rich in monounsaturated fatty acids and antioxidants. We wanted to investigate the effect of HO on lipid levels and prooxidant-antioxidant status in rabbits fed a high-cholesterol (HC) diet. An HC diet caused significant increases in lipids and lipid peroxide levels in the plasma, liver, and aorta together with histopathological atherosclerotic changes in the aorta. Glutathione levels, glutathione peroxidase, and glutathione transferase activities decreased significantly, but superoxide dismutase activity and vitamin E and C levels remained unchanged in the livers of rabbits following HC diet. HO supplementation reduced plasma, liver, and aorta lipid peroxide levels and aorta cholesterol levels together with amelioration in atherosclerotic lesions in the aortas of rabbits fed an HC diet, without any decreasing effect on cholesterol levels in the plasma or liver. HO did not alter the antioxidant system in the liver in the HC group. Our findings indicate that HO reduced oxidative stress and cholesterol accumulation in the aortas of rabbits fed an HC diet.     

Zinc supplementation inhibits lipid peroxidation and the development of atherosclerosis in rabbits fed a high cholesterol diet

Developing atherosclerotic lesions in hypercholesterolemic rabbits are depleted in zinc, while iron accumulates. This study examined the influence of zinc supplementation on the development of atherosclerosis and used isotope dilution gas chromatography-mass spectrometry techniques to measure biomarkers of oxidative lipid damage in atherosclerotic rabbit aorta. Our previous method for F(2)-isoprostane measurement was adapted to include the quantitation of cholesterol oxidation products in the same sample. Two groups of New Zealand white rabbits were fed a high cholesterol (1% w/w) diet and one group was also supplemented with zinc (1 g/kg) for 8 weeks. Controls were fed a normal diet. Zinc supplementation did not significantly alter the increase in total plasma cholesterol levels observed in animals fed high cholesterol. However, in cholesterol-fed animals zinc supplementation significantly reduced the accumulation of total cholesterol levels in aorta which was accompanied by a significant reduction in average aortic lesion cross-sectional areas of the animals. Elevated levels of cholesterol oxidation products (5,6-alpha and beta cholesterol epoxides, 7beta-hydroxycholesterol, 7-ketocholesterol) in aorta and total F(2)-isoprostanes in plasma and aorta of rabbits fed a cholesterol diet were significantly decreased by zinc supplementation. Our data indicate that zinc has an antiatherogenic effect, possibly due to a reduction in iron-catalyzed free radical reactions.     

The effect of thymosin fraction 5 on lipid peroxidation in rabbits fed a high-cholesterol diet

Plasma and erythrocyte lipid levels and susceptibility of erythrocytes to lipid peroxidation were determined in rabbits fed diet containing 2% (w/w) cholesterol, for 3 months. Hypercholesterolemic rabbits had high plasma and erythrocyte lipid peroxide levels as compared to control rabbits. After high-cholesterol diet, the rabbits in the experimental group were divided into two groups. The first group was fed a normal diet for 21 days and the second group was given normal diet plus thymosin F5 injections every other day for the same period. At the end of this period, plasma and erythrocyte lipid peroxide levels were significantly decreased in the group injected with thymosin F5.     

Aqueous extract of Ilex paraguariensis attenuates the progression of atherosclerosis in cholesterol-fed rabbits

Ilex paraguariensis aqueous extract (mate) is an antioxidant-rich beverage widely consumed in South American countries. Here we questioned whether mate could reduce the progression of atherosclerosis in 1% cholesterol-fed rabbits. New Zealand White male rabbits (n = 32) were divided into four groups: control (C, n = 5), control-mate (CM, n = 5), hypercholesterolemic (HC, n = 11) and hypercholesterolemic-mate (HCM, n = 11). The daily water and mate extract consumption was approximately 400 ml. After 2 months of treatment, mate intake did not change the lipid profile or hepatic cholesterol content of control or hypercholesterolemic rabbits (p < 0.05). However, the atherosclerotic lesion area was considerably smaller in the hypercholesterolemic-mate group (HCM, 35.4% vs. HC, 60.1%; p < 0.05). In addition, the aortic cholesterol content was around half that of the HC group (HCM, 36.8 vs. HC, 73.9 microg/mg of protein, p < 0.05). In spite of this, the thiobarbituric acid-reactive substances (TBARS) in the atherosclerotic aorta, liver and serum, and the activity of the antioxidant enzymes in liver and aorta did not differ among groups (p > 0.05). The results showed that Ilex paraguariensis extract can inhibit the progression of atherosclerosis in cholesterol-fed rabbits, although it did not decrease the serum cholesterol or aortic TBARS and antioxidant enzymes.     

Preliminary observations, at the ultrastructural level, on the reactivity of cerebral arteries from New Zealand rabbits to combined atherogenic stimuli (hypercholesterol diet and hypertension)

Both in monkeys (Rhesus and Cynomolgus) and in New Zealand rabbits fed an atherogenic diet, a marked delay in the appearance of atherosclerotic lesions of the cerebral arteries in comparison with other arterial districts has been observed. This appearance has been described in monkeys as relatively earlier if hypertension is added to the atherogenic diet. Preliminary observations on a little group of rabbits on a 3 months hypercholesterolic diet, subjected to Goldblatt aortic coarctation, have shown an increase of blood pressure and a severe gross atherosclerotic involvement of aorta, resembling the one obtainable after 6 months of atherogenic diet. Histologically, the aorta predominantly shows lesions of the fatty streaks type with necrotic areas in the deep; the carotid lesions show some lipid in smooth muscle cells disseminated in a sub-endothelial "edematous" space (rich in protein). The cerebral arteries do not show any lesion. At TEM, the aortic lesions look sometimes as advanced plaques with an initial fibrosis at the surface; the carotid lesions are characterized by a granular deposit in the sub-endothelial space in which some smooth muscle cells (with lipid in the cytoplasm) are present; in the cerebral arteries only the presence of collagen fibers among the smooth muscle cells of the media, never observed in the animals fed the atherogenic diet alone, has sometimes been noted.     

Effects of the calcium channel blocker amlodipine on serum and aortic cholesterol,lipid peroxidation,antioxidant status and aortic histology in cholesterol-fed rabbits

Reactive oxygen metabolites and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of atherosclerosis. Amlodipine, a unique third-generation dihydropyridine-type calcium channel blocker, seems to exert atheroprotective effects through its antioxidant properties related to its chemical structure and independent of its calcium channel-blocking effect. In this study, the interactions of amlodipine with major cellular antioxidants were investigated in order to elucidate the mechanisms underlying its atheroprotective effects. New Zealand white male rabbits were fed regular chow (group 1), chow with 1% cholesterol (group 2), regular chow plus 5 mg/kg/day amlodipine per os (group 3) and 1% cholesterol plus amlodipine (group 4) for 8 weeks. Total cholesterol, malondialdehyde (MDA) and vitamin E concentrations and catalase and superoxide dismutase (SOD) activities were determined in blood drawn before and after the experimental period. Aortic tissue was examined for atherosclerotic changes and aortic total cholesterol, MDA, catalase and SOD were determined. At the end of the 8-week treatment period, serum total cholesterol and plasma MDA were elevated in groups 2 and 4. In group 2, serum vitamin E and plasma SOD diminished (p < 0.05) and catalase increased (p < 0.05). In group 4, SOD activity increased at the end of treatment. MDA levels were lower and plasma SOD activities were higher in group 4 than in group 2. Aortic tissue investigations revealed higher total cholesterol and MDA concentrations and catalase activities in group 2 than in group 4, and the highest tissue SOD activity was recorded in group 4 (p < 0.05 for all comparisons). Morphological examination of aortic tissues exhibited endothelial disarrangement and lipid deposition in group 2. Histopathological alterations related to atherogenesis were less in group 4 than in group 2. Amlodipine seems to exert atheroprotective effects by reducing aortic cholesterol accumulation and blood and aortic lipid peroxidation, enhancing SOD activity both in blood and aortic tissue and suppressing the consumption of vitamin E. On the other hand, the suppression of catalase activity in blood and the aorta interferes with the drug's well-known antioxidant effects.     

Cilostazol inhibits accumulation of triglyceride in aorta and platelet aggregation in cholesterol-fed rabbits

Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities.     

Effects of recombinant human macrophage colony-stimulating factor on atherosclerotic lesions established in the aorta of high cholesterol-fed rabbits

Anti-atherosclerotic effects of human macrophage colony-stimulating factor were investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous aortic plaques. They were then administered 80 microg/kg/day of either macrophage colony-stimulating factor or human serum albumin, as a control, for the next 12 weeks. Compared with the control group, rabbits treated with macrophage colony-stimulating factor had significantly fewer plaques on the inner surface of the thoracic and abdominal aortae, and half the sectional area of thickened intima in the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage colony-stimulating factor also decreased the cholesterol content of the atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony-stimulating factor increased the levels of high density lipoprotein-cholesterol significantly, without influencing other lipid parameters such as the level of low density lipoproteins. The effects of macrophage colony-stimulating factor were evident until the fourth week of drug injection, at which time anti-human macrophage colony-stimulating factor antibodies were clearly induced in the serum. These results indicate that exogenously administered macrophage colony-stimulating factor suppresses atherosclerotic lesions induced by a high cholesterol diet by activating lipid metabolism in vivo.     

Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic acid

Oxidative stress is one of the major risk factors for coronary artery disease. Ellagic acid is a phenolic compound present in fruits and nuts, and has been found to have antioxidative property. Twenty-four New Zealand white (NZW) rabbits were assigned randomly into four dietary groups. The normal group was fed regular rabbit chow, and the cholesterol group was fed a high fat and cholesterol diet. The ellagic acid (E) group and probucol group were fed the same diet as the cholesterol group plus the addition of 1% (w/w diet) ellagic acid and probucol, respectively. Oxidative stress [as measured by plasma lipids, oxygen free radicals and thiobarbituric acid reactive substances (TBARS)] increased in the cholesterol group compared with the normal group; however, it decreased in the probucol and E groups compared with the cholesterol group. Forty-five percent of the intimal surface of the thoracic aorta was covered with atherosclerotic lesions in the cholesterol group, but only 2-3% was covered in the E and probucol groups. The aortic level of 8-(OH)dG and the expression of caspase-8, caspase-9 and Fas ligand were also suppressed after ellagic acid supplement. These results indicated that ellagic acid could prevent atherosclerosis via suppression of oxidative stress and apoptosis in hyperlipidemic rabbits.     

Reduction of atherosclerosis by the peroxisome proliferator-activated receptor alpha agonist fenofibrate in mice

Several clinical and angiographic intervention trials have shown that fibrate treatment leads to a reduction of the coronary events associated to atherosclerosis. Fibrates are ligands for peroxisome proliferator-activated receptor alpha (PPARalpha) that modulate risk factors related to atherosclerosis by acting at both systemic and vascular levels. Here, we investigated the effect of treatment with the PPARalpha agonist fenofibrate (FF) on the development of atherosclerotic lesions in apolipoprotein (apo) E-deficient mice and human apoA-I transgenic apoE-deficient (hapoA-I Tg x apoE-deficient) mice fed a Western diet. In apoE-deficient mice, plasma lipid levels were increased by FF treatment with no alteration in the cholesterol distribution profile. FF treatment did not reduce atherosclerotic lesion surface area in the aortic sinus of 5-month-old apoE-deficient mice. By contrast, FF treatment decreased total cholesterol and esterified cholesterol contents in descending aortas of these mice, an effect that was more pronounced in older mice exhibiting more advanced lesions. Furthermore, FF treatment reduced MCP-1 mRNA levels in the descending aortas of apoE-deficient mice, whereas ABCA-1 expression levels were maintained despite a significant reduction of aortic cholesterol content. In apoE-deficient mice expressing a human apoA-I transgene, FF increased human apoA-I plasma and hepatic mRNA levels without affecting plasma lipid levels. This increase in human apoA-I expression was accompanied by a significant reduction in the lesion surface area in the aortic sinus. These data indicate that the PPARalpha agonist fenofibrate reduces atherosclerosis in these animal models of atherosclerosis.     

Atherosclerotic lesion-specific copper delivery suppresses atherosclerosis in high-cholesterol-fed rabbits

Dietary cholesterol supplements cause hypercholesterolemia and atherosclerosis along with a reduction of copper concentrations in the atherosclerotic wall in animal models. This study was to determine if target-specific copper delivery to the copper-deficient atherosclerotic wall can block the pathogenesis of atherosclerosis. Male New Zealand white rabbits, 10-weeks-old and averaged 2.0 kg, were fed a diet containing 1% (w/w) cholesterol or the same diet without cholesterol as control. Twelve weeks after the feeding, the animals were injected with copper-albumin microbubbles and subjected to ultrasound sonication specifically directed at the atherosclerotic lesions (Cu-MB-US) for target-specific copper delivery, twice a week for four weeks. This regiment was repeated 3 times with a gap of two weeks in between. Two weeks after the last treatment, the animals were harvested for analyses of serum and aortic pathological changes. Compared to controls, rabbits fed cholesterol-rich diet developed atherosclerotic lesion with a reduction in copper concentrations in the lesion tissue. Cu-MB-US treatment significantly increased copper concentrations in the lesion, and reduced the size of the lesion. Furthermore, copper repletion reduced the number of apoptotic cells as well as the content of cholesterol and phospholipids in the atherosclerotic lesion without a disturbance of the stability of the lesion. The results thus demonstrate that target-specific copper supplementation suppresses the progression of atherosclerosis at least in part through preventing endothelial cell death, thus reducing lipid infiltration in the atherosclerotic lesion.     

Urotensin II Promotes Atherosclerosis in Cholesterol-Fed Rabbits

Urotensin II (UII) is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P = 0.013). Atherosclerotic lesions were increased by 24% in the aortic arch (P = 0.005), 11% in the thoracic aorta (P = 0.054) and 18% in the abdominal aorta (P = 0.035). These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits.     

Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet

Background

Mice deficient in the LDL receptor (Ldlr ^−/− mice) have been widely used as a model to mimic human atherosclerosis. However, the time-course of atherosclerotic lesion development and distribution of lesions at specific time-points are yet to be established. The current study sought to determine the progression and distribution of lesions in Ldlr ^−/− mice.

Methodology/Principal Findings

Ldlr-deficient mice fed regular chow or a high-fat (HF) diet for 0.5 to 12 months were analyzed for atherosclerotic lesions with en face and cross-sectional imaging. Mice displayed significant individual differences in lesion development when fed a chow diet, whereas those on a HF diet developed lesions in a time-dependent and site-selective manner. Specifically, mice subjected to the HF diet showed slight atherosclerotic lesions distributed exclusively in the aortic roots or innominate artery before 3 months. Lesions extended to the thoracic aorta at 6 months and abdominal aorta at 9 months. Cross-sectional analysis revealed the presence of advanced lesions in the aortic sinus after 3 months in the group on the HF diet and in the innominate artery at 6 to 9 months. The HF diet additionally resulted in increased total cholesterol, LDL, glucose, and HBA1c levels, along with the complication of obesity.

Conclusions/Significance

Ldlr-deficient mice on the HF diet tend to develop site-selective and size-specific atherosclerotic lesions over time. The current study should provide information on diet induction or drug intervention times and facilitate estimation of the appropriate locations of atherosclerotic lesions in Ldlr ^−/− mice.     

Antibody against cholesteryl ester transfer protein (CETP) elicited by a recombinant chimeric enzyme vaccine attenuated atherosclerosis in a rabbit model

The recombinant chimeric enzyme of AnsB-TTP-CETPC, which comprised asparagianse, tetanus toxin helper T-cell epitope and CETP B-cell epitope, was used to vaccinate New Zealand white rabbits in alum adjuvant. After anti-CETP antibodies were successfully produced, rabbits were fed with a high cholesterol diet for fifteen weeks until atherosclerotic lesions formed in arteries. The results showed that after CETP was inhibited by anti-CETP antibodies the fraction of plasma cholesterol in HDL increased and the fraction of plasma cholesterol in LDL decreased in rAnsB-TTP-CETPC immunized rabbits. The average size of aorta atherosclerotic plaques in rabbits treated with rAnsB-TTP-CETPC was 42.3% less than in rabbits treated with OVA (neutral control), or 47.6% less than in rabbits treated with rHSP 65 (negative control). The average thickness of hyperplastic coronary artery in rAnsB-TTP-CETPC immunized rabbits was 159+/-12 microm, which was significantly lower than in rHSP 65 immunized rabbits (187+/-15 microm) or OVA immunized rabbits (248+/-18 microm). The data reported here demonstrated that rAnsB-TTP-CETPC could significantly attenuate the development of atherosclerosis in rabbits fed with high cholesterol diet, and might be developed to an anti-atherosclerosis vaccine in the future.     

A HMG-CoA reductase inhibitor improved regression of atherosclerosis in the rabbit aorta without affecting serum lipid levels: possible relevance of up-regulation of endothelial NO synthase mRNA.

We determined the role of Fluvastatin: HMG-CoA reductase inhibitor on the regression of atherosclerosis following removal of dietary cholesterol. Male rabbits fed a 0.5% cholesterol diet for 12 weeks were divided into three groups: A1, hypercholesterolemic; A2, fed a regular diet for an 12 additional weeks; and A3, fed a regular diet with fluvastatin (2 mg/kg/day). Fluvastatin treatment (A3) did not affect serum lipid levels compared with A2. However, it decreased the atherosclerotic area in the aortic arch and decreased total and esterified cholesterol concentrations in the descending aorta. Tone-related basal NO release in the thoracic aorta was larger in A3 than in A2. eNOS mRNA in vessel was determined by competitive RT-PCR assay. It increased in A1, compared with normal aorta and decreased in A2; however, it did not decrease in A3. This is the first report of a decrease in eNOS mRNA in atherosclerosis after removal of dietary cholesterol and a reversal of it by a HMG-CoA reductase inhibitor, which may contribute to the regression of atherosclerosis.     

动脉粥样硬化小型猪三磷酸 腺苷结合盒转运体 A1 表达的变化

用贵州小香猪建立动脉粥样硬化动物模型,探讨动脉粥样硬化小型猪三磷酸腺苷结合盒转运体 A1(ABCA1) 表达的变化 . 采用血管内膜损伤法加高脂高胆固醇饲料喂养贵州小香猪,建立动脉粥样硬化动物模型 . 血浆总胆固醇、甘油三酯和高密度脂蛋白胆固醇的浓度均用氧化酶法测定,采用逆转录聚合酶链反应检测 ABCA1mRNA 水平,蛋白质印迹和免疫组织化学检测 ABCA1 蛋白质的表达 . 喂养 12 个月后,实验组与正常对照组比较,空腹血浆总胆固醇、甘油三酯和高密度脂蛋白胆固醇水平升高;实验组小型猪主动脉、髂动脉、颈总动脉和冠状动脉可见动脉粥样硬化斑块和脂质条纹;实验组小型猪肝组织、主动脉、小肠组织 ABCA1 表达上调 . 结果提示,采用血管内膜损伤法加高脂高胆固醇饲料喂养小型猪可建立动脉粥样硬化动物模型 . 动脉粥样硬化小型猪肝组织、主动脉和小肠组织 ABCA1 表达上调 .     

Attenuation of lipid peroxidation and hyperlipidemia by quercetin glucoside in the aorta of high cholesterol-fed rabbit

Antioxidative activity of dietary flavonoids is suggested to be, at least partly, responsible for a wide variety of their biological effects relating to anti-atherosclerosis. However, it is not known whether dietary flavonoids reach to the target site and act as antioxidants. In this study, we tried to evaluate the antioxidative effect of quercetin 3-O-beta-D-glucoside (Q3G), a typical flavonoid present in vegetables, in rabbit aorta. New Zealand White rabbits were fed a control diet (control group), 2.0% cholesterol diet (HC group) and 2.0% cholesterol plus 0.1% Q3G (HC + Q3G group) for one month. The amounts of total cholesterol, triacylglycerol and total fatty acids in both the plasma and aorta were significantly lower in the HC + Q3G group as compared with the HC group. Quercetin was detected in the aorta of the HC + Q3G group after enzymatic deconjugation, indicating that quercetin accumulated as conjugated metabolites in the aorta. The contents of TBA-reacting substances (TBARS) and cholesteryl ester hydroperoxides (CEOOH) in the aorta of the HC + Q3G group were significantly lower than those in the HC group. The aorta of HC + Q3G group was more resistant than that of HC group in copper ion-induced lipid peroxidation ex vivo. HC + Q3G group accumulated a higher amount of vitamin E per total cholesterol than HC group in the aorta. These results strongly suggest that quercetin glucosides accumulate in the aorta as their metabolites and attenuate lipid peroxidation occurring in the aorta, along with the attenuation of hyperlipidemia.     

Prevention of hypercholesterolemia and atherosclerosis in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail by taurine supplementation

The effects of taurine supplementation on the serum cholesterol levels and the progression of atherosclerosis were investigated in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail. The ingestion of a high-cholesterol diet containing 1% cholesterol by LAP quails for 60 days resulted in a marked elevation in serum non-HDL cholesterol and triglyceride, as well as severe aortic lesions with lipid droplets. An immunohistochemical study showed that the lesion consisted of mainly lipid-rich macrophages and T cells. Sixty-day taurine supplementation (1% in drinking tap water) to LAP quails fed high-cholesterol diet containing 1% cholesterol significantly reduced serum non-HDL cholesterol from 4,549 to 2,350 mg/dl. The serum triglyceride level also decreased after taurine supplementation from 703 to 392 mg/dl. Although the HDL cholesterol level significantly decreased due to the high-cholesterol diet, it recovered to the control level fed a regular diet in response to taurine. Bile acid production was stimulated and hepatic cholesterol was reduced by taurine supplementation. A quantitative analysis using aortic cross-sections showed that areas of oil-red O positive lipid accumulation significantly decreased by 74% after taurine supplementation. These results demonstrated the lipid-lowering and anti-atherosclerotic effects of taurine in a diet-induced hyperlipidemic LAP quail model. The prevention of atherosclerosis by taurine is mainly attributed to an improvement in the serum cholesterol and triglyceride levels, which may be related to changes in the hepatic cholesterol metabolism.