Hypercholesterolemic Diet Research Articles

The beneficial effects of almond (Prunus amygdalus Batsch) hull on serum lipid profile and antioxidant capacity in male rats.

Almond hull is produced in high amounts and mostly used as livestock feed. This study was designed to examine the impact of almond hull powder (AHP) administration on lipid profile and antioxidant activities in plasma and liver in hyperlipidemic rats. As the first step, the antioxidant capacity and radical scavenging activity of AHP were determined using calorimetric methods. Then 36 adult male Wistar rats were randomly divided into 6 groups: group 1 with oral administration of 10% AHP, group 2 with oral administration of 20% AHP, group 3 with oral administration of 30% AHP, group 4 as a positive control with a high cholesterol diet, group 5 as a negative control with a normal diet, and group 6 as a sham group with a normal diet and 20% AHP. The rats were fed a hypercholesterolemic diet to create a hyperlipidemia rat model and then they received AHP for 30 days. Antioxidant and radical scavenging activity of the AHP extract showed a high content of antioxidants that exert potent radical scavenging activity. According to the results obtained, upon the administration of AHP the levels of cholesterol and triglycerides significantly decreased, while the antioxidant capacity of plasma increased. AHP with bioactive compounds and fiber can reduce total cholesterol and triglycerides and improve serum antioxidant capacity.

Aktivitas Hipolipidemik dan Indeks Aterogenik yang Rendah Ekstrak Air Daun Tapak Dara pada Tikus Hiperkolesterolemia

Catharanthus roseus is one plant recognized as medical potential which can decrease cholesterol. Thepresent study was carried out to evaluate the effect of aqueous leaf extracts of C. roseus on plasma lipidprofil levels in rats cholesterol rich diet and atherogenic index. This study was carried out on 15 SpraqueDawley male rats randomly distributed into five groups (n=3). Rats hypercholesterolemic wereadministrated cholesterol rich diet containing 1% (w/w). Normal control group with normal diet whitoutextracts (K1), positive control hypercholesterolemic group (K2) with cholesterol rich diet whitout extracts,and others three groups (K3-K5) were feed high cholesterol and 1 mL of aqueous leaf extracts of C. roseuswith a dose of 20% (w/v), 40% (w/v) and 80% (w/v) respectively, administered twice daily 1 mL orally.Treatment was given for 28 days. After treatment, the plasma lipids profile such cholesterol total, highdensity lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TGA) level were measured. Theresults showed that during the period of treatment with cholesterol rich diet have produced under condition hypercholesterolemic of rats with average cholesterol levels of 124.33 ± 4.04 mg/dL (K2 group). Treatmentwith extract dose of 80% showed the best results among the other doses in reducing levels of total cholesterol,triglycerides, LDL and raise HDL levels. Extract treatment dose of 80% up to four weeks resulted incholesterol total (79.33±3.51 mg/dL), TGA (72.33±6.65 mg/dL), HDL (55.00±3.60 mg/dL), and LDL(9.87±5.34mg/dL). In addition, value ratio of cholesterol:HDL was 1.4: 1 and atherogenic index value was0.44. These results suggest that extracts of leaf C. roseus optimum doses 80% (w/v) has hipolipidemicactivity in hypercholesterolemic rats and it has low atherogenic index value.

Study of oxidative and inflammatory parameters in LDLr-KO mice treated with a hypercholesterolemic diet: Comparison between the use of Campomanesia xanthocarpa and acetylsalicylic acid

Background: Atherosclerosis is an inflammatory disease that affects the arterial wall leading to myocardial, cerebral, and peripheral ischemic syndromes. The use of low doses of aspirin inhibits platelet aggregation and inflammation and prevents cardiovascular mortality. However, ASA may produce hemorrhagic events. Thus, several studies have sought new natural compounds to suppress platelet aggregation without causing serious adverse effects. Purpose: In this sense, this study aims to compare the effects of Campomanesia xanthocarpa plant extract with those of acetylsalicylic acid (ASA) on inflammatory parameters observed in homozygous mice knockout for the low-density lipoprotein receptor (LDLr-KO) treated with a hypercholesterolemic diet. Material and Methods: In this study, 28 male LDLr-KO mice were divided into three groups and fed a hypercholesterolemic diet for 4 weeks. Thereafter, the animals that received the hypercholesterolemic diet were treated for 5 days with (1) distilled water, (2) C. xanthocarpa extract, or (3) acetylsalicylic acid. The levels of inflammatory markers were assessed in the blood samples. The gastric tolerability of the animals after oral administration of the treatments was assessed through quantification of the lesions in the gastric mucosa. Results: The levels of proinflammatory cytokines IL-1, IL-6, TNF-α, and INF-γ were reduced to 19.2 ± 3%, 20.4 + 1.3%, 24.7 ± 1.2%, and 20.8 ± 1.7%, respectively, in the group treated with C. xanthocarpa, when compared to control group. Furthermore, treatment with plant extract significantly increased the levels of the anti-inflammatory cytokine IL-10 by 27.3 ± 5.9%, but ASA showed no significant effect on the same cytokines when compared to the control group, with the exception of IL-10, which presented an increase of 8.6 ± 3.5%. Treatments with C. xanthocarpa and ASA also caused significant reductions of 26.4 ± 3% and 38.4± 6% in the serum levels of oxLDL, respectively. However, only treatment with C. xanthocarpa reduced the levels of anti-oxLDL antibodies when compared with the control (25.8 ± 6%). In addition, the analyzed extract did not induce ulcerogenic activity, while ASA induced the formation of lesions. Conclusion: In conclusion, treatment with C. xanthocarpa causes anti-inflammatory activity in hypercholesterolemic animals, with results superior to those obtained with the use of ASA.

Hypercholesterolemia and Ecto-enzymes of Purinergic System: Effects of Paullinia cupana.

Hypercholesterolemia is a metabolic disorder characterized by high levels of low-density lipoprotein and blood cholesterol, causing inflammatory lesion. Purinergic signaling modulates the inflammatory and immune responses through adenine nucleotides and nucleoside. Guaraná has hypocholesterolemic and antiinflammatory properties. Considering that there are few studies demonstrating the effects of guaraná powder on the metabolism of adenine nucleotides, we investigated its effects on the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase activity in lymphocytes of rats with diet-induced hypercholesterolemia. The rats were divided into hypercholesterolemic and normal diet groups. Each group was subdivided by treatment: saline, guaraná powder 12.5, 25, or 50 mg/kg/day and caffeine concentration equivalent to highest dose of guaraná, fed orally for 30 days. An increase in adenosine triphosphate hydrolysis was observed in the lymphocytes of rats with hypercholesterolemia and treated with 25 or 50 mg/kg/day when compared with the other groups. The hypercholesterolemic group treated with the highest concentration of guaraná powder showed decreased ecto-adenosine deaminase activity compared with the normal diet groups. Guaraná was able to reduce the total cholesterol and low-density lipoprotein cholesterol to basal levels in hypercholesterolemic rats. High concentrations of guaraná associated with a hypercholesterolemic diet are likely to have contributed to the reduction of the inflammatory process.

Effects of glucomannan/spirulina-surimi on liver oxidation and inflammation in Zucker rats fed atherogenic diets.

Cholesterolemia is associated with pro-oxidative and proinflammatory effects. Glucomannan- or glucomannan plus spirulina-enriched surimis were included in cholesterol-enriched high-saturated diets to test the effects on lipemia; antioxidant status (glutathione status, and antioxidant enzymatic levels, expressions and activities); and inflammation biomarkers (endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α)) in Zucker fa/fa rats. Groups of eight rats each received diet containing squid-surimi (C), squid-surimi cholesterol-enriched diet (HC), glucomannan-squid-surimi cholesterol-enriched diet (HG), or glucomannan-spirulina-squid-surimi cholesterol-enriched diet (HGS) over a period of 7 weeks. HC diet induced severe hyperlipemia, hepatomegalia, increased inflammation markers, and impaired antioxidant status significantly (at least p < 0.05) vs. C diet. HG diet decreased lipemia and liver size and normalized antioxidant status to C group levels, but increased TNF-α with respect to HC diet (p < 0.05). In general terms, 3 g/kg of spirulina in diet maintained the positive results observed in the HG diet but, in addition, increased inflammation index [eNOS/(eNOS + iNOS)] and decreased plasma TNF-α (both p < 0.05). In conclusion, glucomannan plus a small amount of spirulina blocks negative effects promoted by hypercholesterolemic diets. Although more studies are needed, present results suggest the utility of including glucomannan and/or spirulina as functional ingredients into fish derivates to be consumed by people on metabolic syndrome risk.

High doses of garlic extract significantly attenuated the ratio of serum LDL to HDL level in rat-fed with hypercholesterolemia diet.

BackgroundHypercholesterolemia is associated with an increased risk of heart disease. In this study, we investigated the antihyperlipidemic effects of garlic (Allium sativum L.) in rat models of hypercholesterolemic.MethodsWistar male rats were randomly divided into 4 diet groups with garlic supplementation. Male Wistar rats were fed by standard pellet diet (group I), standard diet supplemented with 4 % garlic (group II), lipogenic diet (containing sunflower oil, cholesterol and ethanol) equivalent to 200 mg raw garlic/kg body weight (raw) (group III) and lipogenic diet equivalent to 400 mg raw garlic/kg body weight (raw) (group IV).ResultsRats fed 400 g/kg garlic extract(GE), had a significantly lower concentration of serum low-density lipoprotein cholesterol (LDL-C) cholesterol and elevated HDL –C cholesterol at day 28 (P < 0.05).In addition,serum levels of LDL-C was lower in the III and IV group than those in the IV group (P < 0.001 for each). However, cholesterol efflux capacity was positively correlated with HDL cholesterol concentration (P < 0 · 0001). It was also directly correlated with garlic supplementation (P < 0 · 0001).ConclusionTogether Taken, the results are clearly indicative of the beneficial effects of garlic in reducing lateral side effects of hyperlipidemia. Our data demonstrate that GE has protective effects on HDL in rats with high LDL intake. Therefore, it could be used to remedy hypercholesterolemia with help reduce risk of coronary heart diseaseVirtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1834155749171141

Quality Characteristics of Pan Bread Enriched With Defatted Germinated Pumpkin Seed Flour

The present study was carried out to utilize different levels of germinated pumpkin seed flour (GPSF), as a source of protein and minerals in fortification of wheat flour for making pan bread. Organoleptic properties of prepared pan bread and its biological effect on lipids profile of rats fed on hypercholesterolemic diet were studied. Pan bread was prepared with GPSF at different levels. The results showed a significant decrease in fat content and an increase in protein, fiber contents and caloric value by increasing defatted GPSF replacement level. Biological assay indicated that food intake, protein intake, feed efficiency ratio and protein efficiency ratio of rats were not significantly affected by defatted GPSF replacement. Serum TC, TG and LDL-C were significantly decreased by replacement with 20% defatted GPSF while HDL-C increased and caused a beneficial effect in improving the lipids profile of rats fed on hypercholesterolemic diet.

Effects of dietary oat proteins on cholesterol metabolism of hypercholesterolaemic hamsters

The aim of present study was to investigate the hypocholesterolaemic effects of oat proteins (OP) in hamsters fed with a hypercholesterolaemic diet. The hamsters were divided into five groups and fed with the experimental diets containing oat, OP, oat β-glucan (OG), or OP+OG for 30 days. OP and the OG significantly lowered the concentrations of plasma low-density lipoprotein-cholesterol and liver total cholesterol (TC), and increased the excretion of faecal bile acid and TC. Plasma and liver TC in the OP+OG group were significantly lower than those in the OP or OG groups. Both OP and OG increased the activity of liver cholesterol 7α-hydroxylase (CYP7A1), while its activity in the OP+OG group was strongly increased compared with the OP or OG groups. These results indicated that dietary OP could improve hypercholesterolaemia, while dietary OP and OG together would have better hypocholesterolaemic effects.

Multiplatform metabolomic fingerprinting as a tool for understanding hypercholesterolemia in Wistar rats.

The aim was to investigate the impact of hypercholesterolemic diet on the metabolome of male Wistar rats by a multiplatform metabolomic fingerprinting. Male Wistar rats were fed with two different diets [control (C) and high-cholesterol diet (HC)-containing 2 % cholesterol and 0.5 % cholic acid]. After 7 weeks of experimental feeding, the rats were euthanized for blood collection and plasma recovery. The metabolite fingerprint was then achieved by applying a multiplatform comprising LC-MS, GC-MS and CE-MS. Multivariate statistical analysis showed a clear separation between the C and HC groups. Individual differences in metabolites were evaluated using univariate statistical analysis, and multiple metabolites were identified and confirmed in the plasma. A global profiling integrates for the first time pathways affected by high-cholesterol diet intake and allowed us to elucidate some of the associated alterations underlying the hypercholesterolemia event in Wistar rats. HC feeding stimulated the alteration of multiple pathways in Wistar rats, warning of the risk of developing important diseases, which can be modulated by the diet. Further studies are required to investigate the possibilities to revert or ameliorate the negative effects triggered by HC intake.

Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated by its antioxidant activity

Context: Kombucha (KT) is claimed to have various beneficial effects on human health, but there is very little scientific evidence available in the literature.Objective: The present study investigates the effects of Camellia sinensis (GT) Linn. (Theaceae) and KT, two natural drinks, on cholesterol and antioxidant status using a hypercholesterolemia rat model.Materials and methods: The present study compared the free-radical scavenging abilities and polyphenol levels of GT and KT. Wistar rats fed cholesterol-rich diets were given KT or GT (5 mL/kg body weight per day, po) for 16 weeks, then fasted overnight and sacrificed. The plasma lipid levels, thiobarbituric acid reactive substances (TBARS) and aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (GGT) serum levels, antioxidant activities of superoxide dismutase (SOD) and catalase (CAT), and creatinine and urea rats were examined.Results: KT had a phenolic compound of 955 ± 0.75 mg GAE/g) followed, by GT (788.92 ± 0.02 mg GAE/g). The free radical scavenging activity of KT was higher than GT. Compared with GT, KT induced lowered serum levels of TC, TG, VLDL-C, and LDL-C by 26, 27, 28, and 36%, respectively, and increased the serum level of high-density lipoprotein cholesterol (HDL-C). KT induced a 55% decrease of TBARS level in liver and 44% in kidney, compared with those of rats fed a cholesterol-rich diet alone. Moreover, CAT and SOD activities were reduced by 29 and 33%, respectively, in liver and 31 and 35%, respectively, in kidney, after oral administration of KT, compared with those of HCD-fed rats.Conclusion: The findings revealed that KT administration induced attractive curative effects on hypercholesterolemic, particularly in terms of liver–kidney functions in rats. Its effect on humans needs to be studied further.

Role of IL-18 and its signaling in atherosclerosis

Cardiovascular diseases (CVD) including coronary artery disease (CAD) and stroke are the largest cause of worldwide morbidity and mortality, where atherosclerosis is the underlying pathology. Recent investigations of atherosclerosis have focused on the role of inflammation, providing new insights into the mechanism of the disease. Macrophages and T-lymphocytes present in the atherosclerotic lesions produce a wide array of cytokines that can exert both pro- and anti-inflammatory effects. Pro-inflammatory cytokines of the interleukin category are considered to be key players in the chronic vascular inflammation that is typical for atherosclerosis. Various studies support the concept that interleukin-18 (IL-18) is a pro-inflammatory cytokine with pro-atherogenic properties. Previous data in Apo E-/- mice demonstrated that IL-18 accelerates atherosclerosis via interferon gamma (IFN- γ) and CXCL16 expression. IL-18 acts by binding to its receptor IL-18R complex, a heterodimer containing α (IL-1Rrp) chain responsible for extracellular binding of IL-18 and a nonbinding, signal-transducing β (AcPL) chain. IL-18 binding to IL-18Rα is shown to result in upregulation of IL-1R-associated kinase (IRAK) and TRAF-6, resulting in nuclear translocation of nuclear factor kappa-B (NF-κB). Presence of activated NF-κB is shown in coronary arteries of pigs fed a hypercholesterolemic diet, in rat arterial smooth muscle cells after balloon injury and in unstable coronary atherectomies. Recent work has shown that genes involved in the lipid uptake and cholesterol efflux in macrophages, like peroxisome proliferator-activated receptor-γ (PPAR-γ) and Liver-X-receptor-α (LXR-α) regulate the expression of many key genes that are involved in the development and progression of atherosclerosis e.g. cytokines, matrix metalloproteinases (MMPs) and scavenger receptors (CD36, SR-A, SR-B1). MMP-9/MMP-2 (members of gelatinase family) are shown to be one of the effector genes of these nuclear receptors (PPAR-γ and LXR-α). Specifically, a role of MMP-9 in atherosclerosis, plaque instability and rupture has been demonstrated during arterial lesion progression. Thus IL-18 can be strongly viewed as a proatherogenic and pro-inflammatory cytokine, as IL-18 signaling results in upregulation of various pro-inflammatory genes and development of atherosclerotic lesions, thus could be envisaged as a therapeutic target.

Abstract 250: Oxidative Stress Mediated Increase of HMGB-1 and RAGE cCntributes to Ascending Aortic Aneurysm Development in vivo.

Background: Ascending-Thoracic Aortic Aneurysm (TAA) is a life-threatening condition for which the only treatment available is the surgical replacement/repair of the dilated aorta. It is known that oxidative stress (ROS) plays an important role in aortic wall remodeling involved in TAA: ROS induces pathological changes in vascular smooth muscle cells (VSMC) and triggers a disorganized and excessive production of matrix components and mediators of elastolysis. We demonstrated that chronic infusion of Angiotensin II (AngII) induces TAA formation in mice with concomitant accumulation of both ROS and synthetic VSMC, similar to that seen in human aneurysmal tissues. We also demonstrated that two ROS triggered molecules, the Receptor for Advanced Glycation end product (RAGE) and its ligand HMGB-1/amphoterin, are highly expressed in dysfunctional human aortic tissue. Recently a few microRNAs (miRs) have been proposed to play a role in aneurysm formation. We found that miR-143 is significantly down-regulated in human TAA tissues. We hypothesized that miR-143 may play a role in TAA development by regulating RAGE/HMGB-1 expression. Methods: RAGE and HMGB-1 expression was tested in control and aneurysmal human ascending aorta. C57BL6/J mice were fed a hypercholesterolemic diet and infused with saline or Ang II (1000 ng/kg/min) for 28 days. MiR-143, HMGB-1 and RAGE expression was evaluated by Western blotting and qPCR in murine ascending aorta samples and in human aortic VSMC treated with AngII (100nM) for 4 and 24 hrs. Results: Human aneurysmal aorta shows down-regulation of miR-143 concomitant with up-regulation HMGB-1 and RAGE expression. AngII infusion induces TAA in mice together with up-regulation of HMGB-1 and RAGE and miR-143 down-regulation. AngII treatment of VSMC induces RAGE and HMGB-1 expression and down-regulation of miR-143. A miR target analysis, using bioinformatic miR-mRNA algorithm tools, identified HMGB-1 as a direct target of miR-143. Conclusion: Our data suggest that miR-143, RAGE and HMGB-1 may cooperate in the process of aortic remodeling behind TAA formation. Further studies, investigating the interplay between miR-143 and HMGB-1/RAGE activation, may lead to potential new pharamacological targets for the treatment of TAA.

Naringenin protects cardiac hypercholesterolemia-induced oxidative stress and subsequent necroptosis in rats

In earlier studies, the supplementation of the natural compound Naringenin (NGEN), improved the liver oxidative and inflammatory status, which indicates its direct effect via inhibition of the nuclear factor κB pathway on high cholesterol-induced hepatic damages. In this regard, the present study highlights the mechanisms associated with the protective efficacy of NGEN in the heart tissue of hypercholesterolemic diet rats. The animals exposed to a high cholesterol diet (HCD) for 90 days exhibited a significant increase in the levels of serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities, nitric oxide (NO) levels, protein and lipid oxidative markers and cardiac lipids profile. Moreover, hypercholesterolemia decreased the levels of enzymatic and non enzymatic antioxidants associated with mitochondrial dysfunctions as proved by the decrease in the mitochondrial complexes in comparison to controls. Importantly, cholesterol-feeding significantly increased myocardial reactive oxygen species (ROS) and nuclear DNA damage and led to the activation of gene expression of the tumor necrosis factor-α (TNF-α) and receptor-interacting protein kinase 3 (RIP3) mRNA that contributed to the elucidation of cholesterol-induced necroptosis, a recently described type of programmed necrosis, in the cardiac tissue. Our results show that the co-administration of NGEN (50 mg/kg/bw) in HCD rats improved all the altered parameters and provided insight into a possible molecular mechanism underlying NGEN suppression of necroptosis pathway in the heart.

LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes.

Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5(-/-) mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5(-/-) mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti-inflammatory, pro-survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.

The prevention and treatment effects of egg yolk high density lipoprotein on the formation of atherosclerosis plaque in rabbits.

Atherosclerosis is the main leading cause of cardiovascular diseases. The purpose of this study was to assess the potential preventive effect of egg yolk HDL on the atherosclerosis plaque formation. Thirty rabbits were divided into five groups: A; normal diet, B; hyper-cholesterolemic diet, C; hypercholesterolemic + 400 mg/kg egg yolk HDL D; hypercholesterolemic +100 mg/kg egg yolk HDL and E; 200 mg/kg egg yolk HDL. At the end of the experiment, the lipid profiles were measured by spectrophotometric method. The histological sections of thoracic aorta also were taken and analyzed under light microscope. At the end of the 2(nd) and the 4(th) weeks, there was a significant increase of cholesterol level in groups B, C, and D compared to group A (P<0.05). Following HDL treatment, triglyceride (TG) levels increased significantly versus group A and also the TG level decreased significantly in group C, D, and E versus group B (P<0.01). Egg yolk HDL significantly increased HDL-C in groups C, D, and E (P<0.01) compared to groups A and B (P<0.05). The surface area of the atherosclerotic plaque was increased significantly in group B versus group A (P<0.001). Egg yolk HDL consumption reduced the plaque size significantly (P<0.001). Our findings indicated that treatment with egg yolk HDL increased serum HDL-C and decreased atherosclerotic plaque size in rabbits. Thus, egg yolk HDL may be considered as an anti-atherosclerotic treatment for cardiovascular diseases.

A Lutein Nano‐Emulsion is more Effective than Regular Lutein in Protecting Cholesterol‐Induced Liver Injury by Increasing Lutein Bioavailability in Guinea Pigs

Regular lutein (R‐lutein) vs lutein prepared in nano‐emulsion (NANO) (average particle diameter = 250 nm) were compared on their effects in reducing hepatic steatosis and liver inflammation in guinea pigs with diet‐induced liver injury. Twenty four guinea pigs were divided into 3 groups (8/group) and were fed for 6 weeks either a hypercholesterolemic diet (0.25g/100g dietary cholesterol) only (control) or in combination with 3 mg/d of R‐Lutein or 3 mg/d of lutein as NANO. Plasma lutein was 3 times higher in the NANO group compared to the R‐Lutein group (68.3 vs 22.7 nmol/L, respectively) while there was no detectable plasma lutein in control guinea pigs. Lutein concentrations in liver (p&lt; 0.001), adipose (p&lt; 0.001) and eyes (p&lt; 0.001) were greater in the NANO, intermediate in the R‐Lutein and almost non‐existent in the control group indicating that lutein in NANO is more easily absorbed and delivered to the target tissues. Further, guinea pigs fed NANO lutein had hepatic steatosis scores of 2.04 ± 0.53 which were lower than those found in control (2.50 ± 0.45) or in guinea pigs from the R‐lutein group (2.63± 0.26) (p&lt; 0.025). Inflammatory cytokines, Interleukin (IL)‐1 beta and Monocyte chemoattractant protein‐1 were lower in the NANO group compared to the R‐Lutein or the control groups (p&lt;0.05). These results indicate that utilizing a nano‐delivery mechanism, results in higher lutein bioavailability and a greater protection against hepatic steatosis and inflammation

MP52-13 THE EFFECT OF PARTIAL BLADDER OUTLET OBSTRUCTION (PBOO) SEVERITY AND HYPERCHOLESTEROLEMIA ON ERECTILE FUNCTION IN RATS

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research I1 Apr 2015MP52-13 THE EFFECT OF PARTIAL BLADDER OUTLET OBSTRUCTION (PBOO) SEVERITY AND HYPERCHOLESTEROLEMIA ON ERECTILE FUNCTION IN RATS Serap Gur, Nur Bayatli, and Didem Yilmaz Serap GurSerap Gur More articles by this author , Nur BayatliNur Bayatli More articles by this author , and Didem YilmazDidem Yilmaz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1730AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are commonly coexist and very prevalent in men aged over 50 years. One of the leading theories of this interrelation is atherosclerosis-induced pelvic injury. We investigated the degree of partial bladder outlet obstruction (PBOO) induced by a ligation (with 5F or 4F catheter [c]) of the bladder neck and the role of atherosclerosis induced by hypercholesterolemic diet (HCD) on erectile function in rats. METHODS A total of 96 Sprague-Dawley male rats were divided into 6 groups: 1) Sham-operated; 2) PBOO (5Fc); 3) PBOO (4Fc); 4) HCD 5)HCD-PBOO (5Fc) and 6) HCD-PBOO (4Fc). HCD groups were fed 4% cholesterol and PBOO groups were subjected by ligation of the urethra for 6 wk. Erectile response was measured using cavernosal nerve stimulation by evaluating ratios of intracavernosal pressure (ICP)/mean arterial pressure. The relaxant and contractile properties of corpus cavernosum smooth muscle (CCSM) strips were evaluated in tissue baths. Immunohistochemical (IHC) staining for neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), Rho-activated kinase (ROCK) and collagen deposition was performed. RESULTS The weight of bladder enhanced gradually in obstructed and combination groups and peaked in HCD-PBOO (4F)(Table). Relaxant and contractile responses of CCSM decreased depending on the severity of PBOO with HCD (Table). Rho-kinase inhibitor Y-27632 (10 μM) inhibited peak and sustained contractile responses to phenylephrine in groups (Table). We found lower nNOS, eNOS, higher Rho-kinase and collagen expressions in PBOO and combined groups. CONCLUSIONS The PBOO caused the more marked ED manifesting by considerable lowering of erectile response and the shift HCD in rats promoted. Our results suggest that the PBOO causes the functional and molecular changes, penile remodeling, accumulation of extracellular collagen in penile tissue, which may become more stressed with the HCD. The management of atherosclerosis may be beneficial in the treatment and continued research are needed for PBOO with HCD and will undoubtedly contribute to the future development of novel therapies for LUTS and ED. Sham-control PBOO(5F) PBOO(4F) HCD HCD-PBOO(5F) HCD- PBOO(4F) Bladder weight (g) 0.12 ± 0.01 0.25 ± 0.008*** 0.34 ± 0.004*** 0.53 ± 0.02*** 0.67 ± 0.004***### 0.91 ± 0.01 ***††† ICP/MAP (7.5V) 1.15 ± 0.06 0.66 ± 0.007*** 0.50 ± 0.020*** 0.52 ± 0.010*** 0.32 ± 0.01***### 0.10 ± 0.002***††† ACh (10-3M) 91.5 ± 1.5 78.9 ± 0.7*** 63.7 ± 2.5*** 46.7 ± 1.3*** 18.9 ± 1.1*** ### 6.2 ± 0.2*** ††† EFS relaxation (20Hz) 96.7 ±1.4 86.9 ± 1.6* 70.5 ± 2.1*** 62.6 ± 0.5*** 55.3 ± 1.9***### 16.6 ± 1.6***††† SNP (10-3M) 100 ± 0 100 ± 0 97.4 ± 0.9 91.4 ± 0.3 81.4 ± 0.3*** ### 66.1 ± 0.3*** ††† EFS contraction (40Hz) 69.5 ± 0.2 51.4 ± 0.8*** 43.8 ± 0.1*** 39.6 ± 0.02*** 29.0 ± 0.3***### 18.4 ± 0.9***††† Phe (10-3M) 90.9 ± 4.4 60.3 ± 2.6*** 43.5 ± 1.3*** 36.7 ± 0.8*** 28.1 ± 1.1***### 13.0 ± 1.1***††† Y-27 632(1μM) 100 ± 0 93.8 ± 0.3 43.5 ± 0.2*** 36.7 ± 0.5*** 28.13 ± 1.1***### 13.0 ± 0.8***††† Data are mean ± SEM (n=12-15). *p<0.05, **p<0.01, ***p<0.001 vs sham-control; ###p<0.001 vs PBOO (5F) and †††p<0.001 vs PBOO (4F). © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e632 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Serap Gur More articles by this author Nur Bayatli More articles by this author Didem Yilmaz More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

El ratón deficiente en apolipoproteína E, un modelo traslacional para el estudio de la aterosclerosis

IntroductionAtherosclerosis is one of the leading causes of morbidity and mortality in Western countries and bears several histopathological similarities to chronic inflammation. Mice deficient in apolipoprotein E (apoE-/−) are widely used in the study of the mechanisms involved in the onset and progression of the atherosclerotic lesion. ObjectiveTo evaluate the impact of an atherogenic diet in lesion formation in apoE-/− mice. Material and methodsTwo month-old apoE-/− mice were subjected, or not (controls), to a high fat/high cholesterol diet (10.8% fat, .75% cholesterol) for two months. Lipid profile, lesion formation, and macrophage, lymphocyte, collagen, vascular smooth muscle cells (VSMC), and necrotic core content, were determined within the lesion using histological and immunohistochemical techniques. Leukocyte-endothelial cell interactions were quantified by intravital microscopy in the cremaster microcirculation. ResultsapoE-/− mice subjected to a hypercholesterolemic diet showed increased circulating levels of total cholesterol and triglycerides compared to those subjected to a control diet. These effects were accompanied by a clear development of atherosclerotic lesion in the aorta, which was characterized by enhanced macrophage (Mac3+), lymphocyte (CD3+) collagen, VSMC and necrotic core content. In parallel, increased adhesiveness of leukocytes to the arteriolar endothelium in those animals subjected to an atherogenic diet was also detected. ConclusionThe atherosclerosis model in apoE-/− mice subjected to an atherogenic diet shares common features with the human atherosclerotic lesion, and constitutes an appropriate model to detect new therapeutic targets and evaluate novel developed drugs.

The antiatherogenic effect of bixin in hypercholesterolemic rabbits is associated to the improvement of lipid profile and to its antioxidant and anti-inflammatory effects.

Hypercholesterolemia and oxidative stress have been implicated in the pathophysiology of atherosclerosis and coronary artery disease. We investigated whether the carotenoid bixin (BIX) may reduce oxidative damage, inflammatory response, and the atherosclerotic lesion induced by hypercholesterolemia in rabbits. Rabbits received regular chow (control) or a hypercholesterolemic diet (0.5% cholesterol) alone or supplemented with BIX (10, 30 or 100 mg/kg body weight, b.w.) or simvastatin (15 mg/kg b.w.) for 60 days. Treatment with BIX or simvastatin reduced the atherosclerotic lesions in cholesterol-fed rabbits (up to 55 and 96% reduction, respectively). This protective effect of BIX was accompanied by decrease in the levels of tumor necrosis factor alpha by 15%, interleukin 6 by 19%, lipid peroxidation by 60%, non-high-density lipoprotein cholesterol (non-HDL-C) by 37%, and triglycerides by 41%. BIX increased by 160% the HDL-C levels and decreased by 67% the atherogenic index of hypercholesterolemic rabbits. In atherosclerotic rabbits, the non-protein thiol groups content and the activity of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and thioredoxin reductase were increased in the aortic tissue, whereas paraoxonase activity was reduced in the serum. All these changes were completely prevented by BIX or simvastatin treatment. These results demonstrate that BIX reduces the extent of atherosclerotic lesions and this effect was associated with the decrease in oxidative stress, inflammatory response, and improvement of dyslipidemia, which were most effectively controlled after treatment with 10-30 mg BIX/kg b.w. BIX consumption may, therefore, be an adjuvant to prevent atherosclerosis reducing risk factors for coronary diseases.

LRP5 deficiency down-regulates Wnt signalling and promotes aortic lipid infiltration in hypercholesterolaemic mice.

Low-density lipoprotein receptor-related protein 5 (LRP5) is a member of the LDLR family that orchestrates cholesterol homoeostasis. The role of LRP5 and the canonical Wnt pathway in the vascular wall of dyslipidaemic animals remains unknown. In this study, we analysed the role of LRP5 and the Wnt signalling pathway in mice fed a hypercholesterolaemic diet (HC) to trigger dyslipidaemia. We show that Lrp5−/− mice had larger aortic lipid infiltrations than wild-type mice, indicating a protective role for LRP5 in the vascular wall. Three members of the LDLR family, Lrp1, Vldlr and Lrp6, showed up-regulated gene expression levels in aortas of Lrp5−/− mice fed a hypercholesterolaemic diet. HC feeding in Lrp5−/− mice induced higher macrophage infiltration in the aortas and accumulation of inflammatory cytokines in blood. Wnt/β-CATENIN signalling proteins were down-regulated in HC Lrp5−/− mice indicating that LRP5 regulates the activation of Wnt signalling in the vascular wall. In conclusion, our findings show that LRP5 and the canonical Wnt pathway down-regulation regulate the dyslipidaemic profile by promoting lipid and macrophage retention in the vessel wall and increasing leucocyte-driven systemic inflammation.