Hypercholesterolemic Rabbits Research Articles

Study of steroidal compounds from peel and seed of some pomegranate cultivars (Punica granatum L.) and investigating the effect of pomegranate seed oil on blood lipid levels in hypercholesterolemic rabbits

Study of steroidal compounds from peel and seed of some pomegranate cultivars (Punica granatum L.) and investigating the effect of pomegranate seed oil on blood lipid levels in hypercholesterolemic rabbits

Hypercholesterolemia negatively influences morphology and molecular markers of epithelial cells within the choroid plexus in rabbits

BackgroundChoroid plexus (CP) is an important tissue not only to produce cerebrospinal fluid (CSF) but also to regulate substances that are secreted into or absorbed from CSF through blood–cerebrospinal fluid barrier (BCSFB) formed by CP epithelial cells (CPECs). CPECs display signs of deterioration in aged and diseased people. However, whether CPECs in hypercholesterolemic animals develop such damage is not known.MethodsWe used cholesterol-fed wild-type or Watanabe hereditary hyperlipidemic (WHHL) rabbits of identical age to determine CPEC changes in terms of morphology and protein expression/localization.ResultsCompared with non-cholesterol-fed control rabbits, prolonged exposure to cholesterol reduced CPEC height and increased lipofuscin levels in CPECs, indicating cellular damage. Expression of aquaporin 1 on the apical membranes of CPECs was diminished in cholesterol-exposed rabbits, implying a reduced CSF-producing function in the CP. The rabbit macrophage-specific antibody (RAM11) immunoreaction became positive in CPECs adjacent to foam cells, indicating an alteration in this cell type.ConclusionCholesterol insults from the circulation (which is reflected by foam-cell accumulation in the CP) induce CPEC dysfunction, and the latter seems to be enhanced by foam cells in hypercholesterolemic rabbits.

Natural cocoa improves birth weight and viability of rabbit pups born to hypercholesterolemic mothers

BackgroundMaternal nutrition affects fetal growth and development in humans and animals. Low birth weight can be caused by maternal hypercholesterolemia and is associated with increased risk of cardiovascular and other metabolic diseases later in adult life. Cocoa powder is rich in flavonoids and reduces plasma cholesterol levels. The study investigated the effect of hypercholesterolemia and natural cocoa intake during pregnancy on the birth weight and viability of rabbit pups. MethodsHypercholesterolemic female New Zealand White rabbits were crossed with normocholesterolemic males and randomly grouped into 2 (n = 4 each). One group (HCC) received natural cocoa powder in their water in addition to high cholesterol diet during pregnancy, whereas the other (HC) received only water and high cholesterol diet. Litter size, birth weight and viability of pups were assessed and compared to a control group (NC) fed normal rabbit chow (n = 2). ResultsAverage litter sizes of hypercholesterolemic rabbits (HC and HCC groups) were 3, whereas that of control group, NC was 5. Mean birth weight of pups was significantly lower in offspring of HC (42.73 g, SD 8.47) and HCC (50.0 g, SD 3.54) as compared to NC (73.0 g, SD 5.37). Mortality of offspring was highest in HC group (58.3%) as compared to 50% in HCC. ConclusionsMaternal hypercholesterolemia during pregnancy reduces litter size, birth weight and viability of offspring in rabbits and these deleterious effects may be minimized by regular intake of natural cocoa. Although further studies in humans need to be conducted, the results of this study suggest the need to monitor maternal cholesterol levels during pregnancy and the effects on pregnancy outcomes and health of offspring later in life.

Honokiol, an active compound of Magnolia officinalis, is involved in restoring normal baroreflex sensitivity in hypercholesterolemic rabbits.

This study investigated the effects of methanol extract Magnolia officinalis (MEMO) on baroreceptor reflex sensitivity (BRS) in the hypercholesterolemic rabbits and the involved molecular mechanisms. Male New Zealand white rabbits were randomly divided into Control (normal diet), Cholesterol (0.5% w/w cholesterol diet), and Magnolia groups (0.5% w/w cholesterol diet plus 1% w/w MEMO). The animals were treated with the designated diet for 4 or 8 weeks. BRS in the control of heart rate was assessed by linear regression method. After 8 weeks of treatments, plasma total cholesterol (TC) was significantly elevated in the Cholesterol/Magnolia groups. The arterial blood pressure (aBP) was increased in the Cholesterol and Magnolia groups. The depression of BRS observed in the Cholesterol group was significantly ameliorated in the Magnolia group. After L‐NAME (Nω‐nitro‐Larginine methyl ester, 20 mg/kg, iv), the BRS of the Cholesterol group was significantly improved. Results from our in vitro study further indicated that honokiol, the principle component of MEMO, would protect human umbilical vein endothelial cells (HUVECs) from H2O2‐induced damages and inhibit H2O2‐induced vascular smooth muscles cells (VSMCs) proliferation, which was evident by the decreased expression of pFAK, and p‐Erk1/2. The results of the present study suggested that the improvement of BRS by MEMO in the hypercholesterolemic rabbits might be mediated by the antioxidant property of MEMO as indicated by the results from the L‐NAME and in vitro honokiol studies.

Phytoconstituents of an ethanolic pod extract of Prosopis cineraria triggers the inhibition of HMG-CoA reductase and the regression of atherosclerotic plaque in hypercholesterolemic rabbits

BackgroundThe HMG-CoA reductase is key enzyme of cholesterol biosynthesis which potentially contributes in management of hypercholesterolemia. The present study was designed to assess the inhibitory effect of phytoconstituents of an ethanolic extract of Prosopis cineraria pods on HMG – CoA reductase and regression potential of atherosclerotic plaque.MethodsHealthy, adult male, albino rabbits in which hypercholesterolemia was induced by supplying the high fat diet and a supplement of cholesterol powder with coconut oil (500 mg/5 ml/Day/kg body weight) for 15 days, were used as a disease model. Phytochemical analysis of an ethanolic extract Prosopis cineraria pods was conducted using LCMS, GCMS and FTIR analysis. Further, in-vitro, in-vivo and in-silico assessments were performed.ResultsThe in-vitro assessment of HMG -CoA reductase activity indicated a 67.1 and 97.3% inhibition by the extract and a standard drug (Pravastatin), respectively. Additionally, an in-silico evaluation was made using appropriate docking software and results also indicated as significant interactions of the identified compounds with the target enzyme. Treatment of rabbits with the ethanolic extract of P. cineraria pod resulted in significant (P ≤ 0.001) reductions in total cholesterol, LDL cholesterol, VLDL cholesterol, and triglyceride. Accordingly, reductions were occurred in atherosclerotic plaque, intima and media of aortal wall along with lumen volume of the aorta significantly increased (P ≤ 0.001).ConclusionIt can be illustrating that the ethanolic extract of Prosopis cineraria pod contains potent bioactive phytocompounds might be inhibit HMG – CoA reductase and have regression potential of atherosclerotic plaque.

Cardioprotective properties of fish enriched with bioactive lipids from olive oil by products

AbstractAnti-inflammatory properties of olive oil are partly attributed to the inhibition of the Platelet-Activating Factor (PAF), a potent inflammatory mediator that is implicated in the initiation and prolongation of atherosclerosis. PAF inhibitors also exist in an extract from olive pomace that inhibits development and regression of atherosclerotic plaques in hypercholesterolemic rabbits. On the other hand, fish consumption is recommended for prevention of cardiovascular diseases, leading to a constantly increasing demand for fish supply, which is further enhanced by the rising consumers’ awareness. As a result a significant growth of aquaculture worldwide has been occurred, which among others strives for improving the nutritional value of the produced fish. Important breakthroughs have occurred in the replacement of fish oil, traditionally used, by plant oils in compounded fish feeds contributing to more nutritious fish products. Under this perspective, present work aimed to evaluate the cardioprotective properties of a novel seabream fed with olive pomace extract.In this crossover study, thirty apparently healthy, men and women were randomly assigned in two diet sequences for 8-week duration (6-week washout period between them), consuming either normal or enriched with olive pomace fish, twice a week. The study was approved by the Bioethics Committee of Harokopio University. Dietary intake was assessed with a validated for the Greek population semi-quantitative food-frequency questionnaire. Lifestyle parameters, biochemical factors, P-selectin and Plasminogen-activator inhibitor-1 (PAI-1) levels were determined. In addition, ex-vivo platelet aggregation in platelet-rich plasma against PAF, ADP and thrombin were measured and the results expressed as EC50 values (the concentration of the agonist that cause 50% of maximum aggregation). Also, PAF key metabolic enzymes activities, responsible for PAF levels, were determined.Concerning dietary habits and biochemical markers only total cholesterol revealed a small increase, within the normal range, after enriched fish consumption, compared to baseline levels. Both fishes resulted in higher EC50 (lower platelet sensitivity) values only against PAF without being differentiated (ptime = 0.02, ptrial = 0.9), while PAI-1 levels were only increased after normal fish consumption (p0–8 weeks = 0.01). The ratio of Lipoprotein-Associated-Phospholipase A2 (catabolic enzyme of PAF) to LDL and PAF-CDP-choline:cholinephosphotransferase (biosynthetic enzyme of PAF) were decreased after the enriched (p0–8 weeks = 0.003) and the normal (p0–8 weeks = 0.01) fish consumption, respectively.Seabream fed with olive pomace seems to exhibit cardioprotective properties by decreasing platelet sensitivity against PAF and modulate PAF metabolism.This research has been co-financed by the European Regional Development Fund of the EU and Greek national funds (project code:T1EDK-00687).

Calcitriol modulates cholesteryl ester transfer protein (CETP) levels and lipid profile in hypercholesterolemic male rabbits: A pilot study.

Vitamin D3 efficacy against cardiovascular disease prevention has been reported in many experimental studies. We aimed to investigate the effect of the calcitriol or active form of Vitamin D3 (1, 25(OH) 2D3) on serum cholesteryl ester transfer protein (CETP) levels in a rabbit model of atherosclerosis. New Zealand white male rabbits were fed with 1% cholesterol diet and randomly assigned into two groups (n=6). The case group was administrated with 50000 calcitriol (IU/kg/per wk) and the control group which administrated with calcitriol solvent (sesame oil) for 2 months. Then, after two months the lipid profile, CETP and 25OHD3 levels were measured. The serum concentration of CETP was increased after treatment with calcitriol in case group as compared to the control group (41.75±3.19 vs. 34.5±2.3, ng/ml, P<0.05). We also observed higher levels of the 25OHD3 in the calcitriol group at the 1st month (16.3±1.64 vs. 12.8±1.33ng/ml) and the 2nd month (19.5±2.14 vs. 12.5±1.25ng/ml) as compared with the control group. the significant increase in the level of HDL-C was observed in the case group than the control group (P<0.01). In addition, serum levels of LDL- Cholesterol (LDL-C), Triglyceride (TG) were reduced after assessment at 1st and 2nd month after administration of calcitriol. Our research indicated the significant anti-atherogenic effects of calcitriol in the rabbit model of atherosclerosis. However, increased in CETP levels by calcitriol may know as an additional way, which interfere with the anti-atherogenic effects of calcitriol.

Anti-Atherosclerotic and Anti-Inflammatory Effects of Curcumin on Hypercholesterolemic Male Rabbits.

Curcumin has a potent antioxidant and anti-inflammatory properties that may suppress inflammatory component of atherosclerosis. It has been demonstrated that curcumin derivatives can reduce the formation of arterial fatty streaks in cholesterol-fed rabbits. Therefore in this study we evaluated the protective effects of Curcumin on the progression of atherosclerosis. 20 mature rabbits were included for this study; they were randomly divided into four groups each of 5. Group 1: (normal control) were fed corn pellets diet and tab water, group 2: (high cholesterol diet control) were kept on cholesterol rich diet (2% cholesterol) and tab water. Group 3: (cholesterol and rosuvastatin treated group) were kept on cholesterol rich diet (2% cholesterol) and 2.5mg/kg/day Rosuvastatin dispersed in DW and given orally, group 4: (cholesterol and curcumin treated group) were kept on cholesterol rich diet (2% cholesterol) and 0.2% curcumin added with corn pellets. The study continued for 12weeks then assessment of serum level of high sensitive C-reactive protein, ICAM1, VCAM1 and PCSK9 was carried out at the end of the study. Total antioxidant activity of curcumin was also determined. Histopathological examination of aortic tissues for atherosclerotic changes was also carried out. Atherogenic (cholesterol rich diet) induced an increment in serum level of TC, LDL, VLDL and TG with concomitant decrement in serum level of HDL and increased atherogenic index. Treatment with curcumin produced substantial reduction in serum TC, LDL, TG with no effect on HDL level thus decreased atherogenic index. Rabbits treated with curcumin showed a significant reduction in the serum level of high sensitive C-reactive protein, ICAM1, VCAM, PCSK9 serum expression and aortic total antioxidant capacity. Curcumin has a potent anti-inflammatory and anti- oxidant effects against atherosclerosis so exerts a protective role by decreasing lipid oxidation and inflammatory markers.

Urotensin II and urantide exert opposite effects on the cellular components of atherosclerotic plaque in hypercholesterolemic rabbits.

Increasing levels of plasma urotensin II (UII) are positively associated with atherosclerosis. In this study we investigated the role of macrophage-secreted UII in atherosclerosis progression, and evaluated the therapeutic value of urantide, a potent competitive UII receptor antagonist, in atherosclerosis treatment. Macrophage-specific human UII-transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet for 16 weeks to induce atherosclerosis. Immunohistochemical staining of the cellular components (macrophages and smooth muscle cells) of aortic atherosclerotic lesions revealed a significant increase (52%) in the macrophage-positive area in only male transgenic rabbits compared with that in the nontransgenic littermates. However, both male and female transgenic rabbits showed a significant decrease (45% in males and 31% in females) in the smooth muscle cell-positive area compared with that of their control littermates. The effects of macrophage-secreted UII on the plaque cellular components were independent of plasma lipid level. Meanwhile the wild-type rabbits were continuously subcutaneously infused with urantide (5.4 µg· kg−1· h−1) using osmotic mini-pumps. Infusion of urantide exerted effects opposite to those caused by UII, as it significantly decreased the macrophage-positive area in male wild-type rabbits compared with that of control rabbits. In cultured human umbilical vein endothelial cells, treatment with UII dose-dependently increased the expression of the adhesion molecules VCAM-1 and ICAM-1, and this effect was partially reversed by urantide. The current study provides direct evidence that macrophage-secreted UII plays a key role in atherogenesis. Targeting UII with urantide may promote plaque stability by decreasing macrophage-derived foam cell formation, which is an indicator of unstable plaque.

Bioefficacy of red cabbage against hypercholesterolemic diet mediated oxidative stress

BackgroundThe shift towards hypercaloric diets and sedentariness has raised lifestyle related disorders and escalated health care cost. In order to tackle this epidemiological transition, healthy, affordable food choices should be introduced in the routine menu. In this context, red cabbage is known for its rich phytochemistry, minerals, antioxidant vitamins and dietary fiber. Considering these evidences, red cabbage leaves and its extract were assessed against hypercholesterolemia and associated oxidative stress.MethodsIn bioefficacy assessment trial (12 weeks), there were two dietary regimens; normal and hypercholesterolemic (1% cholesterol) that were further split into three groups each. In both feeding trials, red cabbage leaves (20%) and its extract in dose equivalent to red cabbage leaves were assessed against control diets. At termination of trial, serum lipidemic parameters and oxidative stress biomarkers were assessed to test the efficacy of diets.ResultsIn hypercholesterolemic rabbits, red cabbage leaves showed significant reduction in cholesterol, LDL-c and triacylglycerol levels i.e. 15.19, 18.09 and 9.42% than extract administered groups; 10.79, 12.24 and 5.72, respectively. Besides, red cabbage leaves also portrayed momentous enhancement of superoxide dismutase (SOD) and catalase (CAT) activity up to 13.29 & 17.63% by lowering lipid peroxidation by 27.86% in hypercholesterolemic diet fed groups, whereas red cabbage extract administered group depicted relatively lesser amelioration in lipid peroxidation i.e. 21.42%.ConclusionsRed cabbage leaves possess higher ameliorative potential against altered lipidemic profile and lipid peroxidation as compared to its extract thus explains its ability to prevent exhaustion of endogenous antioxidant enzymes; SOD and CAT.

P4482Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers

Abstract Background/Introduction Hypertension is highly prevalent in NAFLD patients (39%). NAFLD has been independently associated with an increased risk of arterial hypertension in observational studies and emerge as the most frequent cause of chronic hepatic disease in adults. Therefore, we can deduce that treating hypertension in NAFLD carriers will be often necessary. However, there are no established criteria for choosing the most appropriate drug therapy for hypertension in patients with NAFLD, and the basic research may be the first step to the development of these criteria. Purpose We aimed to evaluate the effects of the renin-angiotensin system blockade with angiotensin-converting enzyme inhibitor ramipril and angiotensin 2 type 1 receptor antagonist olmesartan, used preventively, in NAFLD induced in rabbits fed hypercholesterolemic diet. Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers. Methods Olmesartan study: Thirty-four rabbits were divided into three groups (control, untreated and olmesartan). The untreated and olmesartan group were fed a hypercholesterolemic diet. Animals from olmesartan group were treated with olmesartan 1mg/kg/day. Ramipril study: Twenty-nine rabbits were divided into three groups (normal, placebo, and ramipril). The placebo and ramipril groups were fed a hypercholesterolemic diet. The groups were orally administered 0.35 mg/kg/day of ramipril, and an equivalent volume of vehicle was administered to the placebo group. In both studies, at the end of the 8th week, all rabbits underwent segmental hepatic resection and were euthanised. Blood samples were collected to determine glucose, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and aminotransferase levels at baseline and euthanasia. Haematoxylin and eosin and Gomori trichrome stained slides were analysed based on the histological scoring system for NAFLD. Results The comparison between two groups (olmesartan with untreated group and ramipril with placebo) showed that ramipril and olmesartan significantly diminished the development of steatosis (p&lt;0.013, p=0.032), lobular inflammation (p&lt;0.001, p=0.006), and fibrosis (p=0.015, p=0.02). Based on NAFLD activity score, olmesartan and ramipril significantly reduced the development of nonalcoholic steatohepatitis (p&lt;0.001, p=0.003). Conclusion(s) The preventive use of olmesartan and ramipril attenuates the development of hepatic steatosis, lobular inflammation and fibrosis in hypercholesterolemic rabbits. These results can serve as the basis to the establishment of criteria for choosing the most appropriate drug therapy for hypertension in NAFLD carriers.

Natural cocoa inhibits maternal hypercholesterolaemia-induced atherogenesis in rabbit pups.

Atherosclerosis begins during foetal development and is enhanced by maternal hypercholesterolaemia during pregnancy. This study assessed the effect of natural cocoa on atherosclerosis in offspring conceived in maternal hypercholesterolaemia. Female rabbits were fed a cholesterol-enriched diet for two weeks and hypercholesterolaemia was confirmed, after which they were crossed with normocholesterolaemic males. One group of hypercholesterolaemic mothers (HCC) received natural cocoa powder (NCP) in their drinking water, whereas the other group (HC) received only water. Histological analysis of three segments of the aorta (arch, thoracic and abdominal) from offspring of both groups was compared with a control group (NC). Intima-media thickness of the aortic arch in offspring born to hypercholesterolaemic rabbits (HC: 146 µm) was higher compared to HCC (99 µm) and control rabbits (58.5 µm). All the sections from the aortic arch of the HC group had atherosclerotic lesions while none of the sections of the aortic arch from the NC and HCC groups had lesions present. Inferentially, regular and voluntary consumption of NCP during pregnancy may inhibit aortic atherogenesis in offspring of hypercholesterolaemic mothers.

Cardiac inflammation and diastolic dysfunction in hypercholesterolemic rabbits.

BackgroundLeft ventricular diastolic dysfunction (LVDD) is present in more than 50% of patients suffering from heart failure. LVDD animal models are limited and its underlying mechanisms remain largely unknown. Aortic valve stenosis (AVS) may cause LVDD, and we recently reported LVDD in an AVS rabbit model. Here we aimed to develop a rabbit model of LVDD without AVS.MethodsRabbits were fed with a 0.5% cholesterol-enriched diet (n = 9) or normal diet (n = 8) until they developed LVDD defined by a value of the echocardiographic parameter E/Em ratio higher than the mean at baseline + 2SD. Rabbits were then fed a 0.2% cholesterol-enriched diet for 4 weeks (average total diet duration: 20 weeks). Detailed cardiac structure and function measurements were assessed by echocardiography at baseline, weeks 8, 12 and 14 to 20, when applicable. Histological analyses and RT-qPCR were performed on LV samples.ResultsThe hypercholesterolemic diet induced LVDD without systolic dysfunction or AVS, as shown by multiple echocardiographic parameters, including early filling mitral peak velocity and deceleration rate, Em/Am ratio and E/Em ratio (all p<0.05), and by increased cardiac mRNA expression of brain natriuretic peptide (Bnp). Cardiac expression of mRNA for Nox2, Vcam1, Mmp12, Mmp12/Timp1, Il1b and Col1/Col3 ratios was also higher in these rabbits (p<0.05). In contrast, cardiac Sod2 mRNA expression was reduced in hypercholesterolemic rabbits compared to controls.ConclusionRabbits fed with a cholesterol-enriched diet develop LVDD with preserved systolic function and evidence of cardiac inflammation and oxidative stress. This rabbit model may be used in future studies to test treatment strategies against LVDD.

Infusions of Large Synthetic HDL Containing Trimeric apoA-I Stabilize Atherosclerotic Plaques in Hypercholesterolemic Rabbits

BackgroundAmong strategies to reduce the remaining risk of cardiovascular disease, interest has focused on using infusions of synthetic high-density lipoprotein (sHDL). MethodsNew Zealand rabbits underwent a perivascular injury at both carotids and were randomly allocated into 2 protocols: (1) a single-dose study, where rabbits were treated with a single infusion of sHDL containing a trimeric form of human apoA-I (TN-sHDL, 200 mg/kg) or with Placebo; (2) a multiple-dose study, where 4 groups of rabbits were treated 5 times with Placebo or TN-sHDL at different doses (8, 40, 100 mg/kg). Plaque changes were analysed in vivo by intravascular ultrasound. Blood was drawn from rabbits for biochemical analyses and cholesterol efflux capacity evaluation. ResultsIn both protocols, atheroma volume in the Placebo groups increased between the first and the second intravascular ultrasound evaluation. A stabilization or a slight regression was instead observed vs baseline in the TN-sHDL-treated groups (P < 0.005 vs Placebo after infusion). TN-sHDL treatment caused a sharp rise of plasma-free cholesterol levels and a significant increase of total cholesterol efflux capacity. Histologic analysis of carotid plaques showed a reduced macrophage accumulation in TN-sHDL-treated rabbits compared with Placebo (P < 0.05). ConclusionsOur results demonstrate that acute and subacute treatments with TN-sHDL are effective in stabilizing atherosclerotic plaques in a rabbit model. This effect appears to be related to a reduced intraplaque accumulation of inflammatory cells. Besides recent failures in proving its efficacy, sHDL treatment remains a fascinating therapeutic option for the reduction of cardiovascular risk.

Regular transient limb ischemia prevents atherosclerosis progression in hypercholesterolemic rabbits.

Background:Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits.Methods:Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test.Results:Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = –2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = –2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = –2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = –2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049).Conclusion:In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.

A comparative study of anti-atherosclerotic/anti-inflammatory effect of irbesartan and rosuvastatin in hypercholesterolemic male rabbits

Objective: To evaluate the potential protective effect of irbesartan on atherosclerotic progression using rosuvastatin as a positive control.&#x0D; Methods: Twenty local domestic rabbits were randomly divided into four groups, five rabbits per each group. The first group (I), rabbits were receiving normal diet; the second group (II), rabbits were receiving 2 % cholesterol diet; the third group (III), rabbits were receiving rosuvastatin and 2% cholesterol diet and; the fourth group (IV), rabbit were receiving irbesartan and 2% cholesterol diet. Serum level of cholesterol, triglycerides, LDL, VLDL and HDL were determined after 12 weeks of the study. Serum level of high sensitive C-reactive protein, ICAM1and VCAM1 were measured after 12 weeks of the study. Total antioxidant activity was also determined. Aortic tissue sent for histopathological examination of atherosclerosis lesion.&#x0D; Result: Data of this study have showed that atherogenic diet caused an increase in serum level of TC, LDL, VLDL and TG and a decrease in serum level of HDL. Treatment of rabbits with irbesartan caused substantial decrease in serum lipid profile compared with untreated rabbit receiving atherogenic diet. No significant difference was seen between irbesartan- and rosuvastatin-treated rabbits in all lipid parameters measured with the exception that the HDL level in rosuvastatin-treated rabbits was significantly higher than that of irbesartan-treated rabbits. Rabbit treated with irbesartan showed a significant decrease in the serum level of high sensitive C-reactive protein, ICAM1, VCAM1 and aortic total antioxidant capacity when compared with untreated group. No significant difference was seen between irbesartan- and rosuvastatin-treated rabbits in all these inflammatory parameters measured. Histopathological examination showed that irbesartan decreased atherogenic lesion significantly when compared with untreated rabbits.&#x0D; Conclusion: Irbesartan has a potential protective effect against atherosclerosis via decreasing lipid oxidation and inflammatory mediators. In terms of lipid lowering and anti-inflammatory effects, irebsartan has similar pattern of effectiveness to rosuvastatin.

Effects of Paeoniflorin on the activity of muscle strips, intracellular calcium ion concentration and L‑type voltage‑sensitive calcium ion channels in the sphincter of Oddi of hypercholesterolemic rabbits.

Sphincter of Oddi dysfunction (SOD) is a benign obstructive disorder predominantly resulting from spasms of the SO. Pharmacological therapies aim to induce SO relaxation; the hypercholesterolemic (HC) rabbit is the only SOD model available for study. In the present study, SO muscle strips, intracellular calcium ion concentrations and the mRNA expression levels of the α1C subunit of the L‑type calcium channel in the SO muscle cells of HC rabbits were employed to investigate the effects of paeoniflorin (PF). Alterations in L‑type calcium channel α subunit 1C mRNA and protein expression in SO cells with HC following the application of different concentrations of PF were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. The whole cell patch clamp technique was used to observe the effects of different concentrations of paeoniflorin on L‑type calcium channel current. The results of the present study demonstrated that PF induced the relaxation of SO muscle strips and reduced the intracellular calcium concentration in the SO muscle cells of HC rabbits. In addition, PF decreased the mRNA expression levels of the α1C subunit of the L‑type calcium channel and reduced the L‑type calcium channel current in SO cells. These results suggested that the mechanism underlying the relaxation of the SO muscle by PF may be associated with the reduction of calcium ion influx via L‑type calcium channels.

Effect of green tea on obesity and serum lipid profiles in both normo- and hyper-cholesterolemic rabbits

Obesity has been linked with several comorbidities like cardiovascular disorders, diabetes, and hypertension. Weight reduction is directly associated with the consumption of green tea. So, with this premise of background, we evaluated the potential of green tea consumption on obesity and serum lipid profiles in both normo- and hyper-cholesterol emic rabbits. Sixty New Zealand white rabbits (age: 6-8 months; weight 1.5-2 kg) were used for this experiment. Rabbits were randomized and equally divided into three different groups. Group I (control group) received 10 ml/kg of distilled water twice daily, Group II received high cholesterol diet twice daily, and Group III received high cholesterol diet along with green tea solution 10 ml/kg, twice daily for 90 days. Weight measurements and serum analysis were conducted on Day 0 and day 90. For the obtained data, SPSS analysis was performed (SPSS 21). A significant increment of body weight was observed in control (1.97 ± 0.12 vs 2.87 ± 0.21, p&lt;0.0001) and high cholesterol groups (1.91 ± 0.23 vs 3.13 ± 0.31, p&lt;0.0001) at Day 90 when compared with Day 0. Though the results were not significant, there was a reduction in the body weight in the green tea group (2.20 ± 1.47 vs 1.72 ± 0.22) at Day 90 when compared with Day 0. Consumption of green tea for 90 days resulted in weight loss and inhibition of the increase in the levels of TC, LDL, and VLDL. So, green tea can act as a natural food supplement for the management of obesity and dyslipidemia.

Olive oil addition to the high-fat diet reduces methylglyoxal (MG-H1) levels increased in hypercholesterolemic rabbits

Olive oil addition to the high-fat diet reduces methylglyoxal (MG-H1) levels increased in hypercholesterolemic rabbits

Close Association of Myeloperoxidase-Producing Activated Microglia with Amyloid Plaques in Hypercholesterolemic Rabbits.

Microglial activation and oxidative stress have been linked to the formation of amyloid plaques found in Alzheimer's disease (AD). Epidemiologic and experimental evidence also suggests that cholesterol (CH) contributes to the pathogenesis of AD, particularly the formation of amyloid plaques. We have previously described the development of amyloid-β (Aβ) plaques in New Zealand white rabbits maintained on a 0.125%-0.25% w/w CH diet for extended periods of time (28 months). Here we further characterize this model with combined immunofluorescence and immunohistochemical staining to evaluate markers of immune cell activation. Five out of eight CH-fed rabbits, but not control rabbits, developed extracellular Aβ plaques in both the hippocampus and cortex. Significantly (p < 0.05) higher CD11b microglial staining was found in the hippocampus, temporal cortex, and frontal cortex of CH-fed versus control rabbits. In the temporal cortex and parietal cortex, active CD-11b- and ferritin-positive microglia were found in close proximity to Aβ plaques. Classification and quantification of activated microglia in the temporal cortex showed that 68±12.9%, 25±7.3%, and 7±2.7% of all microglia had a primed, reactive, and amoeboid phenotype, respectively. Activated microglia also expressed myeloperoxidase which was co-localized to amyloid deposits. Our findings in this dietary-based model lend further support of a role of activated microglia and oxidative stress during the development of AD and strengthens the links between hypercholesterolemia, inflammatory status, and AD.