Reduction of oxidative stress and atherosclerosis in hyperlipidemic rabbits by Dioscorea rhizome

Hyperlipidemia may induce oxidative stress, which is important in the pathogenesis of atherosclerosis. Dioscorea rhizome (DR) is the powdered form of yams, and possesses antioxidant and hypolipidemic function. We therefore investigated the antioxidative and antiatherogenic effects of DR on hyperlipidemic rabbits. The control group was fed chow containing 0.5% cholesterol and 10% corn oil. The probucol and DR groups were fed the same diet as the control group but with the addition of 100 mg probucol/kg chow and 200 mg DR/kg chow, respectively. Total cholesterol and triacylglycerol plasma levels, RBC hemolysis T50, lucigenin chemiluminescence, and luminol chemiluminescence increased in the control group compared with the normal group, and decreased in the probucol and DR groups compared with the control group. The activity of antioxidant enzymes superoxide dismutase and catalase was significantly higher in the probucol and DR group than in the control group. The level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in liver DNA was lower in the probucol and DR group than in the control group. Eighty percent of the intimal surface of the thoracic aorta was covered with atherosclerotic lesions in the control group but only 40% of the surface was covered in the DR group. These results suggest that supplementation with DR reduces oxidative stress and attenuates atherosclerosis in hyperlipidemic rabbits.     

Vitamin E supplementation alters HDL-cholesterol concentration and paraoxonase activity in rabbits fed high-cholesterol diet: comparison with probucol

Vitamin E and probucol are well-known antioxidants that prevent cells from the oxidative stress, which is a risk factor of atherosclerosis. Male rabbits were fed either 0.03% vitamin E or 0.05% probucol in a 0.5% high-cholesterol (HC) diet for 8 weeks. Vitamin E and probucol significantly suppressed an increase in plasma total-cholesterol (total-C) and low-density lipoprotein cholesterol compared to HC-control group. However, plasma high-density lipoprotein-cholesterol (HDL-C) and HDL-C/total-C ratio levels and plasma paraoxonase activity were only significantly higher in vitamin E group after 8 weeks. Hepatic ACAT activity was significantly lower in both vitamin E and probucol groups than in HC-control group, while HMG-CoA reductase activity was the highest only in the probucol group. Total fecal sterol content was significantly higher in probucol and vitamin E groups than in the two control groups. Some atherogenic signs were discovered in the aortic fatty streak of HC-control group, yet not in other groups. Hepatic mRNA expressions of apo B-100 and apo C-III were significantly lower in probucol group than in other groups. Vitamin E supplementation was found to alter the plasma HDL-C-related factors; meanwhile, probucol supplementation was very effective in enhancing cholesterol metabolism, except for a negative effect that reduced plasma HDL-C concentration.     

Putative mechanisms of action of probucol on high-density lipoprotein apolipoprotein A-I and its isoproteins kinetics in rabbits

Probucol is a widely prescribed lipid-lowering agent, the major effects of which are to lower cholesterol in both low- and high-density lipoproteins (LDL and HDL, respectively). The mechanism of action of probucol on HDL apolipoprotein (apo) A-I kinetics was investigated in rabbits, with or without cholesterol feeding. 125I-labeled HDL was injected intravenously, and blood samples were taken periodically for 6 days. Kinetic parameters were calculated from the apo A-I-specific radioactivity decay curves. Fractional catabolic rate (FCR) and synthetic rate (SR) of apo A-I in rabbits fed a normal chow and normal chow with 1% probucol were similar. Apo A-I FCR of the rabbits fed 0.5% cholesterol was significantly increased but there were no changes in SR, compared to findings in the normal chow-fed group. Apo A-I FCR of the rabbits fed 1% probucol with 0.5% cholesterol (both 1 month and 2 months) was significantly increased compared to findings in rabbits fed the normal chow as well as 0.5% cholesterol diet group, while SR of apo A-I was significantly reduced in the former groups. Kinetics at 1 month after discontinuation of 1% probucol (under cholesterol feeding) showed a similar FCR of HDL-apo A-I to that of the rabbits fed 0.5% cholesterol, but the SR of apo A-I remained lower. Apo A-I isoproteins kinetics assessed by autoradiography of isoelectric focusing slab gels showed that the synthesis of proapo A-I was significantly reduced in the 1% probucol with 0.5% cholesterol administered, compared to the 0.5% cholesterol group. Thus, the action of probucol on HDL apo A-I kinetics was only prominent in case of higher serum cholesterol levels. The decreased HDL or apo A-I seen with probucol was apparently the result of an increase in FCR and a decrease in SR of HDL-apo A-I. A decreased synthesis of apo A-I remained evident even 1 month after discontinuing probucol. The action of probucol on the intracellular synthetic processes of apo A-I was revealed by the reduced synthesis of proapo A-I.     

Comparative effects of pitavastatin and probucol on oxidative stress, Cu/Zn superoxide dismutase, PPAR-gamma, and aortic stiffness in hypercholesterolemia

Reactive oxygen species-scavenging enzyme Cu/Zn superoxide dismutase (SOD) regulated by peroxisome proliferator-activated receptors (PPARs) plays an important role in vascular responsiveness. However, it remains unknown whether statin restores vascular dysfunction through the activation of reactive oxygen species-scavenging enzymes in vivo. We hypothesized that pitavastatin restores vascular function by modulating oxidative stress through the activation of Cu/ZnSOD and PPAR-gamma in hypercholesterolemia. New Zealand White male rabbits were fed either normal chow or a 1% cholesterol (CHO) diet for 14 wk. After the first 7 wk, the CHO-fed rabbits were further divided into three groups: those fed with CHO feed only (HC), those additionally given pitavastatin, and those additionally given an antioxidant, probucol. The extent of atherosclerosis was assessed by examining aortic stiffness. When compared with the HC group, both the pitavastatin and probucol groups showed improved aortic stiffness by reducing aortic levels of reactive oxidative stress, nitrotyrosine, and collagen, without affecting serum cholesterol or blood pressure levels. Pitavastatin restored both Cu/ZnSOD activity (P < 0.005) and PPAR-gamma expression and activity (P < 0.01) and inhibited NAD(P)H oxidase activity (P < 0.0001) in the aorta, whereas probucol inhibited NAD(P)H oxidase activity more than did pitavastatin (P < 0.0005) without affecting Cu/ZnSOD activity or PPAR-gamma expression and activity. Importantly, Cu/ZnSOD activity was positively correlated with the PPAR-gamma activity in the aorta (P < 0.005), both of which were negatively correlated with aortic stiffness (P < 0.05). Vascular Cu/ZnSOD and PPAR-gamma may play a crucial role in the antiatherogenic effects of pitavastatin in hypercholesterolemia in vivo.     

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.     

Effect of dietary fish oil, vitamin E, and probucol on renal injury in the rat

Dietary fish oil, vitamin E, and probucol have been considered in a variety of human and experimental models of kidney disease. Using subtotal nephrectomized cholesterol-fed rats as a model for progressive kidney disease, we examined the effect of 5% dietary fish oil, or a combination of 5% dietary fish oil with 500 IU vitamin E/kg diet or 1% probucol on renal injury. Three-month-old Sprague Dawley rats were fed a control diet (C group) or a cholesterol supplemented (2%) diet (Ch group) containing either fish oil (FO group) or fish oil plus vitamin E (FO+E group) or fish oil plus probucol (FO+P group). After 4 weeks of dietary treatment, the right kidney was electrocoagulated and the left kidney nephrectomized. After 8 weeks, 24-hour urine was collected before sacrifice. No effect of the dietary treatments was noted on serum creatinine, blood urea nitrogen, or proteinuria, except that proteinuria was highest in FO+P group. Rats receiving the cholesterol diets had higher serum low density lipoprotein (LDL) + very low density lipoprotein (VLDL) cholesterol (P < 0.05). In contrast, rats in the FO+P group had the lowest serum total cholesterol and LDL+VLDL cholesterol among all groups. The FO group had 26% lower kidney alpha-tocopherol concentrations than the C group. However, inclusion of vitamin E in the diet (FO+E group) increased the kidney alpha-tocopherol status to a level comparable to that in the C group, whereas inclusion of probucol in fish oil diet (FO+P group) did not improve the kidney alpha-tocopherol status. Rats fed the cholesterol diet had a 2.5-fold higher glomerular segmental sclerosis (GSS) score and 1.5-fold higher glomerular macrophage (GM) subpopulation than the C group. These effects of the cholesterol diet were ameliorated by a fish oil diet (FO group: GSS by 30%, GM by 24%). The inclusion of vitamin E in the fish oil diet (FO+E group) did not further improve the GSS score or GM subpopulation. However, inclusion of probucol in fish oil diet (FO+P group) lowered the GSS score by 73% and reduced GM subpopulation by 83% compared with the Ch group. These remarkable changes can be attributed to the powerful hypocholesterolemic activity of probucol. Our findings indicate that progression of glomerular sclerosis in the rat remnant kidney model of progressive kidney disease can be significantly modulated with fish oil treatment.     

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.     

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.     

Effect of a taurine treatment on the regression of existing atherosclerotic lesions in rabbits fed on a high-cholesterol diet

We studied whether taurine has any regressive effect on existing atherosclerotic lesions and lipid peroxidation in rabbits fed on a high-cholesterol (HC) diet. The cholesterol, triglyceride, malondialdehyde (MDA) and diene conjugate (DC) levels, as well as the aortic histopathological findings were examined in rabbits that had been fed on a cholesterol-containing diet for 8 months [0.5% cholesterol (w/w) for 3 months and subsequently 0.25% cholesterol (w/w) for 5 months], and then for a further 4 months on a normal diet with or without taurine treatment [1% (w/v) in the drinking water]. High levels of lipid and lipid peroxide induced by the HC diet were observed to decline in the plasma, liver and aorta of atherosclerotic rabbits, as well as a slight retardation in aortic atherosclerotic lesions during the regression period. Although no significant differences in the lipid and lipid peroxide levels in the plasma and aorta were found between the regressed groups with or without the taurine treatment, the extent of atherosclerotic lesions in the aorta was less in the taurine-treated regressed group than in the non-treated regressed group. However, the liver MDA and DC levels were lower in the regressed rabbits with the taurine treatment in the non-treated group. These results indicate that the taurine treatment may accelerate the regression of cholesterol-induced atherosclerotic lesions in rabbits without having any effect on the plasma and aorta lipid and lipid peroxide levels.     

Effect of dietary inclusion of Lactobacillus acidophilus ATCC 43121 on cholesterol metabolism in rats

This study examined the effects of Lactobacillus acidophilus ATCC 43121 (LAB) on cholesterol metabolism in hypercholesterolemia-induced rats. Four treatment groups of rats (n = 9) were fed experimental diets: normal diet, normal diet+LAB (2 x 10(6) CFU/day), hypercholesterol diet (0.5% cholesterol, w/w), and hypercholesterol diet + LAB. Body weight, feed intake, and feed efficiency did not differ among the four groups. Supplementation with LAB reduced total serum cholesterol (25%) and VLDL + IDL + LDL cholesterol (42%) in hypercholesterol diet groups, although hepatic tissue cholesterol and lipid contents were not changed. In the normal diet group, cholesterol synthesis (HMG-CoA reductase expression), absorption (LDL receptor expression), and excretion via bile acids (cholesterol 7 alpha-hydroxylase expression) were increased by supplementation with LAB, and increased cholesterol absorption and decreased excretion were found in the hypercholesterol diet group. Total fecal acid sterols excretion was increased by supplementation with LAB. With proportional changes in both normal and hypercholesterol diet groups, primary bile acids (cholic and chenodeoxycholic acids) were reduced, and secondary bile acids (deoxycholic and lithocholic acids) were increased. Fecal neutral sterol excretion was not changed by LAB. In this experiment, the increase in insoluble bile acid (lithocholic acid) reduced blood cholesterol level in rats fed hypercholesterol diets supplemented with LAB. Thus, in the rat, L. acidophilus ATCC 43121 is more likely to affect deconjugation and dehydroxylation during cholesterol metabolism than the assimilation of cholesterol into cell membranes.     

Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits.

We previously established that probucol decreases basal expression of VCAM-1 in the aorta of WHHL rabbits and inhibits the up-regulation of VCAM-1 expression that normally accompanies atherogenesis. To determine whether this effect is shared by other antioxidants in vivo, we now investigated whether a structurally unrelated antioxidant, vitamin E, also inhibits arterial VCAM-1 expression and whether the degree of VCAM-1 inhibition correlates with the reduction of atherosclerosis or the antioxidant protection of LDL. Atherogenesis and VCAM-1 mRNA and protein were determined in four groups of NZW rabbits (n = 6;-8) fed 0.5% cholesterol alone or supplemented with 0.1% vitamin E, a low dose (0.04;-0.075%) of probucol yielding the same degree of antioxidant protection of plasma LDL as vitamin E, or a high dose (0.5%) of probucol, and in normocholesterolemic rabbits. After 81 days, extensive atherosclerosis and a greater than 4-fold up-regulation of VCAM-1 mRNA was seen in rabbits on high cholesterol diet, mostly in the intima. Treatment with vitamin E, high-dose probucol, and low-dose probucol significantly decreased VCAM-1 mRNA by 49.0, 74.9, and 57. 5%, respectively, and reduced atherosclerosis in adjacent segments of the thoracic aorta to a similar degree as reported by previous studies. Immunocytochemistry confirmed that lesions of antioxidant-treated animals also contained less VCAM-1 protein. Neither the degree of VCAM-1 inhibition nor the extent of atherosclerosis correlated with the degree of antioxidant protection of plasma LDL.In summary, treatment with structurally unrelated antioxidants conveyed different degrees of antioxidant protection to plasma LDL but significantly reduced VCAM-1 expression in vivo and inhibited atherogenesis. This is consistent with the assumption that antiatherogenic effects of antioxidants may in part be mediated by interference with oxidation-dependent intracellular signaling.     

Effects of atorvastatin therapy on hypercholesterolemic rabbits with respect to oxidative stress, nitric oxide pathway and homocysteine

Hypercholesterolemia is characterized with changes in lipid profile, nitric oxide pathway and oxidative stress markers. This study is designed to evaluate the effects of hypercholesterolemic diet and atorvastatin therapy on oxidative stress, lipid peroxide and thiobarbituric acid reactive substances (TBARS), NO pathway markers, nitric oxide(NO) and asymmetric dimethylarginine (ADMA), homocysteine, and paraoxonase activity (PON1) in rabbits. Twenty rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into 2 groups on the fourth week of the hypercholesterolemic diet. First group was fed with high-cholesterol diet alone, whereas the second group with the same cholesterol diet plus atorvastatin (0.3 mg/kg/day) for 4 weeks. High-cholesterol diet increased total cholesterol, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), ADMA, TBARS and lipid peroxide levels and reduced PON1 activity and NO levels in rabbits. Four weeks of atorvastatin therapy significantly increased HDL-C, PON1 activity and reduced LDL-C, TBARS and lipid peroxide concentrations. Atorvastatin therapy is beneficial in decreasing oxidative stress related with hypercholesterolemia, mainly affecting lipid profile and PON1 activity.     

Effect of baikal skullcap root (Scutellaria baicalensis radix) on cholesterol level and meat quality in rabbits fed a cholesterol rich diet

The aim of this study was to evaluate the effect of the Baikal skullcap root (Scutellaria baicalensis radix) on the cholesterol level and chemical composition of the hind leg muscles of rabbits. Thirty two White New Zealand rabbits were assigned to four groups. Group C consisted of control animals which were fed a basal mixture for rabbits. Group CH received the same basal diet with a 1% (w/w) pure cholesterol supplement. Group CH+SR received the basal diet with two supplements: 1% (w/w) pure cholesterol and 9% (w/w) skullcap root. Group SR received the basal diet with a 9% (w/w) skullcap root supplement. After 6 weeks rabbits were slaughtered and, total cholesterol as well as dry matter, protein, fat, ash and pH24 were determined in samples of hind leg muscles. Using a Baikal skullcap root with hypercholesterolemic diet (group CH+SR) caused significant reduction (P < or = 0.05) in total cholesterol level in comparison with hypercholesterolemic diet (CH group). The addition of Baikal skullcap root to the food of rabbits significantly increased the muscle protein content (P < or = 0.05) in comparison with C and CH groups. Moreover, supplementation with Baikal skullcap root (CH+SR) decreased about 15.6% (P < or = 0.05) fat level in comparison to CH group. No significant effects were seen in dry matter content, ash, and pH24 value of hind leg muscles of experimental rabbits     

Development and partial metabolic characterization of a dietary cholesterol-resistant colony of rabbits

A colony of New Zealand white rabbits has been developed which, when fed a cholesterol-supplemented diet, exhibit unusual resistance to hypercholesterolemia and atherosclerosis, disorders usually observed in normal cholesterol-fed rabbits. When resistant rabbits (RT) were fed a normal low cholesterol diet (ND), their plasma lipoprotein patterns were significantly different from those of normal rabbits (NR) fed the same diet. The low density lipoprotein cholesterol (LDL-c)/high density lipoprotein cholesterol (HDL-c) ratio and LDL-c/very low density lipoprotein cholesterol (VLDL-c) ratio were lower in the resistant rabbits. The hydrated density of HDL of the normal-responsive rabbits was greater than that of the resistant rabbits. LDL from resistant rabbits contained a lower proportion of esterified cholesterol and protein than LDL from normal rabbits. Peripheral mononuclear cells from resistant rabbits bound about 30% more 125I-labeled rabbit LDL than mononuclear cells from normal rabbits. These results demonstrate that the plasma cholesterol levels of these animals is at least partly under genetic control and that compositional differences exist between the major plasma lipoprotein classes of normal and resistant rabbits even during the ingestion of low-cholesterol diet. The results indicate that at least a part of the difference in the cholesterolemic responses between the two rabbit groups is due to an enhanced LDL uptake by the mononuclear cells, and presumably by other somatic cells of the resistant group.     

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.     

Antioxidative activity of naringin and lovastatin in high cholesterol-fed rabbits.

The consumption of a cholesterol-enriched diet increases the degree of lipid peroxidation, which is one of the early processes of atherosclerosis. The aim of this trial was to determine the antioxidative effects of the citrus bioflavonoid, naringin, a potent cholesterol-lowering agent, compared to the cholesterol-lowering drug, lovastatin, in rabbits fed a high cholesterol diet. Male rabbits were served a high-cholesterol (0.5%, w/w) diet or high-cholesterol diet supplemented with either naringin (0.5% cholesterol, 0.05% naringin, w/w) or lovastatin (0.5% cholesterol, 0.03% lovastatin, w/w) for 8 weeks to determine the plasma and hepatic lipid peroxide, plasma vitamin A and E levels, and hepatic hydrogen peroxide levels, along with the hepatic antioxidant enzyme activities and gene expressions. Only the lovastatin group showed significantly lower plasma and hepatic lipid peroxide levels compared to the control group. The naringin supplementation significantly increased the activities of both hepatic SOD and catalase by 33% and 20%, respectively, whereas the lovastatin supplementation only increased the catalase activity by 23% compared to control group. There was no difference in the GSH-Px activities between the various groups. Content of H2O2 in hepatic mitochondria was significantly lower in groups supplemented with lovastatin and naringin than in control group. However, there was no difference in cytosolic H2O2 content in liver between groups. The concentration of plasma vitamin E was significantly increased by the naringin supplementation. When comparing the antioxidant enzyme gene expression, the mRNA expression of SOD, catalase and GSH-Px was significantly up-regulated in the naringin-supplemented group. Accordingly, these results would appear to indicate that naringin, a citrus bioflavonoid, plays an important role in regulating antioxidative capacities by increasing the SOD and catalase activities, up-regulating the gene expressions of SOD, catalase, and GSH-Px, and protecting the plasma vitamin E. In contrast, lovastatin exhibited an inhibitory effect on the plasma and hepatic lipid peroxidation and increased the hepatic catalase activity in high-cholesterol fed rabbits.     

Does a HDL injection reduce the development of serum hyperlipidemia and progression of fatty streaks in cholesterol fed rabbits?

The influences of homologous (rabbit) or heterologous (human) high density lipoprotein (HDL) on the development of serum hyperlipidemia and progression of fatty streaks were studied in cholesterol fed rabbits. Three groups of New Zealand rabbits were fed a 0.5% cholesterol rich diet for 8 weeks. Additionally into these animals the following solutions were injected intravenously two times per week: group 1 (control): saline; group 2: human HDL dissolved in saline; group 3: rabbit HDL dissolved in saline. The animals of group 2 had lower serum cholesterol levels during the dietary period than rabbits of group 1 (p < 0.05) but the surface of intima covered with fatty streaks was the same as in group 1. On the other hand, the serum cholesterol level in rabbits of group 3 was the same as in group 1 during the whole experimental period, but the surface of aorta covered with fatty streaks was significantly lower (p < 0.05) in group 3 than in group 1. The results of this study support the hypothesis of an antiatherogenic action of HDL, which seems to be independent of the influence of HDL on the serum lipids but depends on the source of HDL.     

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.     

Suppression of high lipid diet induced by atherosclerosis sarpogrelate

Sarpogrelate (SP), a serotonin (5‐HT2A) receptor antagonist, is used as an anti‐platelet agent for the treatment of some vascular diseases. SP has been reported to inhibit 5‐HT induced coronary artery spasm, increase in intracellular calcium and smooth muscle cells proliferation. This study was undertaken to test that SP suppresses the development of atherosclerosis due to high cholesterol diet (HCD) by decreasing blood viscosity and oxidative stress. For this purpose, 29 rabbits were divided into four groups: control group (normal diet); normal diet group with SP at the dose of 5 mg/kg/day; HCD group fed 1% cholesterol; and HCD group with SP at the dose of 5 mg/kg/day. After 90 days of the experiment, blood samples were collected and the animals were killed; the thoracic aorta was stained by the Oil Red O staining method. The results indicate that plasma levels of cholesterol, triglycerides and malondialdehyde were increased in rabbits fed HCD. Plasma viscosity and whole blood viscosity were also higher in the HCD group than that in normal diet group. Treatment with SP prevented these alterations induced by HCD whereas this agent had no significant effect in rabbits fed normal diet. Morphological examination of the aorta revealed that SP treatment prevented the formation of foam cells and atherosclerotic plaque. It is suggested that the beneficial effects of SP in atherosclerosis may be due to actions on blood viscosity, lipid levels and oxidative stress.     

Alpha-tocopherol and probucol reduce autoantibody titer to MDA-LDL in hypercholesterolemic rabbits

We considered the hypothesis that antioxidant supplementation that increases aortic antioxidant concentrations would reduce autoantibody titer to MDA-LDL, a measure that may indicate in vivo oxidation. We assessed autoantibody titer to MDA-LDL in rabbits before and after 5 months of treatment with a nutritionally adequate hypercholesterolemic diet alone (control) or supplemented with synthetic alpha-tocopherol or probucol. Aortic cholesterol and antioxidants were assessed at the end of treatment. alpha-Tocopherol supplementation increased the ratio of aortic alpha-tocopherol to cholesterol by 20-30-fold, while probucol supplementation increased the ratio of aortic probucol to cholesterol to 4-13 micromol/mol. Before treatment, MDA-LDL autoantibody titer averaged 5.09 +/- 0.24 with no difference among groups (p =.53 by ANOVA). However, after treatment, autoantibody titers differed among groups (p <.03 by ANOVA). Autoantibody titers were similar in rabbits supplemented with alpha-tocopherol and probucol (3.69 +/- 0.21 and 3.73 +/- 0.48, respectively, p = 0.81), and 26% (p <.009) lower in antioxidant supplemented rabbits than unsupplemented hypercholesterolemic rabbits (5.03 +/- 0.47). There was an inverse J relationship between autoantibody titer after treatment and aortic alpha-tocopherol/cholesterol and probucol/cholesterol, with minimum values for autoantibody titers above 8-10 micromol antioxidant/mmol cholesterol. The results of this study are consistent with inhibition of in vivo intra-aortic oxidation when aortic alpha-tocopherol or probucol exceed 8-10 micro;mol/mmol cholesterol.