Cholesterol-supplemented Diet Research Articles

Effect of Prebiotic, Probiotic Bacteria and Symbiotic Diets Containing Bacillus Coagulans and Gum Arabic on Lipid Profile in Hypercholesterolemic Rats

Purpose: Hypercholesterolemia is a major problem for many societies as well as for health professionals due to the close association between cardiovascular disease and lipid abnormalities. The current study was conducted to determine the effect of prebiotic, probiotic bacteria and symbiotic diets containing Bacillus Coagulans and Gum Arabic on lipid profile in hypercholesterolemic rats.
 Methodology: The spore suspension was prepared and Gum Arabic was purchased as the natural product. 35 male albino rats (170 ± 5 g) were fed a cholesterol-supplemented diet to induce hypercholesterolemia. The rats were divided into 5 groups (n = 7). The group 1: basal diet (negative control), and the other four groups were given hypercholesterolemia diet supplemented with 25% lard and 2% cholesterol for six weeks to induce hypercholesterolemia in rats. They were divided as follows: Group 2: (positive control), Group 3: fed a supplemented basal diet with 5% Gum Arabic (prebiotic), Group 4: fed a supplemented basal diet with coagulase spores, and group 5: fed a basal diet supplemented with 5% Gum Arabic and spores per day of B. coagulans (synbiotic).
 Results: The findings showed a significant increase in the levels of total cholesterol and triacylglycerol (mg/dL) (P<0.05) in (positive control) fed the basic diet (B.D.), compared to (negative control).
 Unique Contribution to Theory, Practice and Policy: The Anti-Inflammatory Theory and The theory of using prebiotics to lower cholesterol and reduce its absorption. This study indicates that the theory used in the study has been validated. The best results that showed significant differences with the negative control group were achieved in the hypercholesterolemia groups treated with Gum Arabic (GA5%), where the highest mean value was recorded (28.54 ± 3.71 mg/dL), which was close to the negative control (36.33 ± 5.00 mg/dL). As for the groups that took B. coagulans and GA 5% + B. coagulans, a decrease in LDL-c, (VLDL-c), AST and AST levels, and the best result recorded was in the group GA 5% + B.coagulans. Histological examinations also showed that the liver sections in the fifth group showed a normal structure, except for slight degeneration of the liver cells. The best result was in the group of GA 5%+ B. coagulans treatment group compared to the other groups.

Ateroprotective effects of Plinia cauliflora in. New Zealand rabbits: beyond the lipid-lowering effect.

Introduction: Plinia cauliflora [Mart.] Kausel (Myrtaceae), popularly known as "jabuticaba," is a fruit species native to Brazil. Despite extensive widespread usage, its antiatherosclerotic properties' impact remains unknown. Thus, the present study aimed to investigate the cardioprotective effects of a preparation obtained from the fruit peels of P. cauliflora (EEPC). Methods: Male New Zealand rabbits received a 1% cholesterol-supplemented diet for 60days. On the thirtieth day, the animals were divided into five experimental groups and received, once a day, by the oral route, the EEPC (10, 30, and 100mg/kg), simvastatin (2.5mg/kg), or vehicle for 30days. At the end of the experimental period, peripheral blood and arterial branch samples were collected. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), malondialdehyde (MDA), nitrotyrosine (NT), nitrite, interleukin 1 beta (IL-1b), interleukin 6 (IL-6), soluble inter-cellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were measured. Moreover, the catalase and superoxide dismutase levels were measured on the arterial samples. Histopathological analysis and arterial morphometry were also performed. Results and discussion: The oral administration of ESEG significantly lowered the levels of lipids in rabbits that were fed a CRD diet. This treatment also adjusted the protective system against oxidation in the arteries by decreasing the oxidation of lipids and proteins. Additionally, the levels of IL-1b, IL-6, sICAM-1, and sVCAM-1 in the bloodstream decreased significantly, and this was accompanied by a reduction of atherosclerotic lesions in all branches of the arteries. The findings suggest that EEPC may be a possible option for additional management of atherosclerosis.

Balancing dietary plant-based lipids and cholesterol to increase fillet omega-3 deposition in rainbow trout (Oncorhynchus mykiss) fed a diet without animal ingredients

We hypothesized that a low phytosterol oil, such as soybean oil, in combination with an α-linolenic acid (ALA) rich oil, such as linseed oil, and supplemental cholesterol could effectively replace fish oil in salmonid feeds. As such, the primary objective was to blend soybean oil with linseed oil and supplemental cholesterol to maintain fish growth and increase de novo production of the omega-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in trout muscle, since EPA and DHA have been identified as beneficial nutrients in human nutrition, and farmed seafood must meet consumer needs and expectations. To accomplish this, we used soy oil for its low phytosterol properties in combination with linseed oil for its n-3 FA content, with and without cholesterol to improve utilization. Upon conclusion of the study, our results did not support our hypothesis. Trout fed plant-based diets containing any amount of soy oil had reduced growth performance. Only fish fed the plant-based diet with 100% linseed oil plus supplemental cholesterol grew as well as both control groups, fishmeal/fish oil and plant meal/fish oil. Dietary cholesterol supplementation increased plasma cholesterol levels and EPA in fillets (P < 0.05). Two-way ANOVA demonstrated that growth performance and muscle EPA content were significantly increased in fish fed cholesterol-supplemented diets. However, expression of genes involved in fatty acid biosynthesis were not enhanced by cholesterol, suggesting a potential disconnect between gene expression and functional activity. Although our hypothesis failed and soybean oil was found to be less accepted by the fish, resulting in lower growth and feed intake, we were successful in developing a high soy-protein diet (35%) with all-plant ingredients using linseed oil and supplemental cholesterol that resulted in equal fish performance to fish fed a fishmeal/fish oil control diet. More research is needed to identify a cost-effective EPA/DHA source to meet consumer needs and expectations for n-3 FA in trout fillets.

Liposomal Phytosterols as LDL-Cholesterol-Lowering Agents in Diet-Induced Hyperlipidemia.

The high blood level of low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for cardiovascular disease. Plant sterols, known as phytosterols (PSs), can reduce LDL-C in a range of 8-14%. The extent of LDL-C reduction depends on its formulation. Encapsulation into liposomes is one formulation strategy to enhance the efficiency of PSs. PSs (campesterol, stigmasterol, and β-sitosterol) have frequently been assessed alone or in combination for their LDL-C-lowering ability. However, one naturally abundant PS, brassicasterol, has not yet been tested for its efficacy. We have previously developed a novel liposomal formulation containing the PS mixture present naturally in canola that is composed of brassicasterol, campesterol, and β-sitosterol. In this work, the efficacy of our novel liposomal PS formulation that includes brassicasterol was assessed in a hamster model. Animals were divided into five groups: (i) liposomal PS in orange juice, (ii) liposomal PS in water, (iii) marketed PS in orange juice, (iv) control orange juice, and (v) control water. The animals were fed a high-fat, cholesterol-supplemented (0.5%) diet to induce hypercholesterolemia. The treatment was administered orally once daily for 4 weeks. Fasting blood samples were collected at baseline, week 2, and week 4. The extent of the reduction of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides was compared among the groups. Liposomal PSs in both orange juice and water significantly reduced LDL-C compared to their controls. Furthermore, the liposomal PS was as effective as a marketed PS-containing product in reducing LDL-C. Liposomal PSs in both orange juice and water showed similar efficacy in LDL-C reduction, highlighting that these vehicles/food matrices do not affect the efficacy of PSs. The liposomal formulation of a natural PS mixture extracted from canola oil, with brassicasterol as a major component, exhibited a significant LDL-C reduction in a hamster model.

Fatty Acid Composition of Plasma and Liver Lipid Components as Influenced by Diet in the Growing Chick

The influence of dietary protein and cholesterol on plasma and liver lipids and on their component fatty acid composition was studied in growing chicks. Increased dietary protein decreased plasma and α-lipoprotein lipid levels and increased liver cholesterol. Cholesterol supplementation elevated plasma and liver lipids but decreased α-lipoprotein lipids. In general, feeding a low-protein or a cholesterol-supplemented diet resulted in similar fatty acid changes. Both treatments resulted in significantly increased oleic and decreased arachidonic acid levels in the plasma cholesterol esters, glycerides and phospholipids. The oleic acid level of the liver lipids was also higher in chicks fed the low-protein or cholesterol-supplemented diets. The dietary treatments tended to decrease linoleic acid levels particularly in the cholesterol ester fraction. The cholesterol ester fraction showed the most consistent changes.

High cholesterol-supplemented diet during gestation and lactation alters liver glycosaminoglycans and associated lipoprotein receptors and results in fat accumulation in adulthood

In utero insults to growing fetus impact its health in adulthood. Glycosaminoglycans (GAGs) are involved in lipoprotein metabolism in the liver and vary both quantitively and qualitatively on feeding adult rats a diet rich in cholesterol. However, no reports are available to show the modulation of GAGs when the offspring are subjected to a high cholesterol diet in gestation and lactation stages. Hypercholesterolemia in pregnant rats was induced by feeding an AIN-93 diet supplemented with 0.5% cholesterol. The pups born to mothers fed with high cholesterol diet showed a significant increase in cholesterol and triglycerides accumulation in the liver. Quantitative changes in sulfated glycosaminoglycans (sGAGs), in particular of heparan sulfate, were observed across the developmental stages. Other players involved in lipoprotein metabolism, namely low-density lipoprotein receptor-related protein 1, apolipoprotein E, and low-density lipoprotein receptor expression levels, also showed differential changes across developmental stages. Interestingly, when pups from hypercholesterolemic mothers were fed a normal diet after weaning until adulthood, a considerable amount of fat accumulation in the liver was observed, implicating fetal exposure to early high cholesterol exposure on long term health.

Dietary Cholesterol Supplements Disturb Copper Homeostasis in Multiple Organs in Rabbits: Aorta Copper Concentrations Negatively Correlate with the Severity of Atherosclerotic Lesions.

Dietary cholesterol causes atherosclerosis along with a reduction of copper concentrations in the atherosclerosis wall. This study was to determine the relationship between aorta copper concentrations and the severity of atherosclerotic lesions as well as copper homeostasis in multiple organs in cholesterol-fed rabbits. Male New Zealand white rabbits, 10-week-old and averaged 2.0 kg, were fed a diet containing 1% (w/w) cholesterol or the same diet without cholesterol as controls. Twelve weeks after the feeding, aortic atherosclerotic lesions, serum cholesterol, and multiple organ copper concentrations were measured. Compared to controls, rabbits fed cholesterol-supplemented diet displayed higher serum cholesterol levels and developed atherosclerosis. Copper concentrations in the cholesterol-fed rabbits were increased in the serum and kidney but decreased in the atherosclerosis wall and multiple organs, including heart, liver, spleen, and lung. Furthermore, aorta copper concentrations negatively correlated, respectively, with the severity of the atherosclerotic lesion (r = - 0.64, p = 0.01), the microscope atherosclerotic lesion area (r = - 0.60, p = 0.02), and the stenosis of the lumen (r = - 0.54, p = 0.04). Dietary cholesterol not only causes atherosclerosis but also disturbs copper homeostasis in multiple organ systems. The negative correlation between aorta copper concentrations and the severity of atherosclerotic lesions suggests a vicious cycle between copper reduction and the pathogenesis of atherosclerosis. These changes in copper homeostasis would be additive to atherosclerosis as a risk factor for cardiovascular disease in humans.

Dietary Fat and Cholesterol Interactively Alter Serum Lipids and Gut Microbiota in Wistar Rats

Effects of dietary fat type on serum lipids and gut microbiota in cholesterol-fed rats were investigated. Forty-eight male Wistar rats were assigned (8/group) into three cholesterol-free (control) diets containing Corn Oil (CO), Sheep Tallow (ST) or Olive Oil (OO) or three cholesterol-supplemented (experimental) diets (COC, STC, OOC) and given ad libtium for nine weeks. Serum lipids, atherogenic indexes and several biological parameters were determined. Total Bacterial Counts (TBC) and seven bacterial groups were assessed. High-density lipoprotein cholesterol was higher (p&lt;0.003) in CO (89.9 ± 6.5 mg/dl) and OO (80.9 ± 3.0 mg/dl) than ST (55.9 ± 4.3 mg/dl). Higher (p&lt;0.05) total cholesterol and atherogenic coefficient were respectively found in OOC (131.4 ± 9.9 mg/dl, 1.20 ± 0.03 mg/dl) and COC (113.6 ± 10.6 mg/dl, 1.46 ± 0.35 mg/dl) than OO (96.4 ± 2.6 mg/dl, 0.19 ± 0.03 mg/dl) and CO (93.6 ± 2.6 mg/dl, 0.04 ± 0.03 mg/dl), but not in STC (95.8 ± 6.5 mg/dl, 0.70 ± 0.20 mg/dl) versus ST (87.0 ± 7.8 mg/dl, 0.60 ± 0.06 mg/dl). Neither fat nor cholesterol affected body weight, food intake, Bacteroidetes, Clostridium cluster IV, Lactobacillus, and Prevotella. Total Bacterial Count, Clostridium Coccoides-Eubacterium rectalae and Bacteroides were respectively higher (p&lt;0.001) in ST (74.0 ± 20.0, 53.1 ± 8.5, 103.6 ± 32.3) than OO (24.8 ± 3.1, 18.9 ± 5.8, 32.3 ± 15.5). Bacteroides was higher (p&lt;0.05) in ST (103.6 ± 32.3) than COC (38.7 ± 7.8), and STC (97.2 ± 13.5) than OO (32.3 ± 15.5) or COC (38.7 ± 7.8). Firmicutes and Clostridium Coccoides-Eubacterium rectalae were respectively lower (p&lt;0.05) in STC (15.3 ± 1.2, 19.0 ± 4.3) and COC (19.0 ± 2.8, 14.4 ± 1.5) than ST (30.3 ± 4.7, 53.3 ± 8.5) and CO (32.7 ± 2.8, 33.0 ± 7.8), but not in OOC (23.5 ± 3.7, 34.4 ± 6.0) versus OO (25.3 ± 4.7, 18.9 ± 5.8).In conclusion, dietary fat and cholesterol alter serum lipids and gut microbiota in an interaction that is likely to have clinical connotations in cholesterol-related disorders.

Novel fatty acyl apoE mimetic peptides have increased potency to reduce plasma cholesterol in mice and macaques

Ac-hE18A-NH2 is a dual-domain apoE mimetic peptide that possesses the putative receptor binding domain from apoE (LRKLRKRLLR, denoted hE; residues 141–150) covalently attached to lipid-associating peptide 18A. Like apoE, Ac-hE18A-NH2 reduces plasma cholesterol in animal models and exhibits anti-inflammatory properties independent of its cholesterol-reducing effect. Ac-hE18A-NH2 has already undergone phase I clinical trials as a lipid-lowering agent. To explore the therapeutic potential more, we designed and synthesized new analogues by linking ɑ-aminohexanoic acid, octanoic acid, or myristic acid to LRRLRRRLLR-18A-NH2 ([R]hE18A-NH2) and examined the cholesterol-lowering potency in animals. The modified peptides effectively reduced plasma cholesterol in apoE-null mice fed standard chow or a Western diet; the myristyl analogue was the most effective. A single administration of the myristyl analogue reduced plasma total and LDL cholesterol in a dose-dependent manner in hypercholesterolemic cynomolgus macaques for up to 1 week despite the continuation of a cholesterol-supplemented diet. The myristyl peptide (7.4 mg/kg) reduced total and LDL cholesterol at 24 h by 64% and 74%, respectively; plasma HDL levels were modestly reduced and returned to baseline by day 7. These new analogues should exhibit enhanced potency at lower doses than Ac-hE18A-NH2, which may make them attractive therapeutic candidates for clinical trials.

The effect of defatted cocoa powder on cholesterol-induced changes of serum lipids in rats

Cocoa has been known for many health benefits, but its lipid-lowering activity still remains unresolved. To investigate effects of varying amounts of defatted cocoa on serum lipids in cholesterol-fed rats. Forty-eight male Sprague-Dawley rats were randomly assigned into four cholesterol-free (control) and four cholesterol-supplemented (experimental) diets containing 0, 1, 2 or 3% defatted cocoa (DC) and given ad libitumto the rats for ten weeks. Serum total cholesterol (TC), low- and very low-density lipoprotein cholesterol (LDL-C and VLDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were quantified, atherogenic index (AI) was calculated, and other biological parameters were assessed. Food intake and body weight did not respond to DC. Compared to 0% DC, 3% DC had the most prominent effect on serum lipids inducing significant fall in LDL-C and TG, and rise in TC/TG in cholesterol-deprived rats, and increase in VLDL-C and AI, and decrease in HDL-C in cholesterol-fed rats. Compared to cholesterol-deprived rats, 3% DC caused significant rise in VLDL-C, AI and TC/TG, and fall in TG in cholesterol-fed rats. This lipid-modifying effect was markedly substantiated by corresponding linear trend responses to DC. Differences in lipid variables of rats fed on DC diets were less evident. Results suggest that, in contrast to cholesterol-free situations, defatted cocoa is seemingly incapable of counteracting the atherogenic effect of cholesterol in rats, perhaps in an interaction that is likely to have clinical implications in cardiometabolic conditions.

The effect of date palm fruit (Phoenix dactylifera L.) on serum lipid and lipoprotein concentrations in rats fed cholesterol- supplemented diet

BACKGROUND: The date palm fruit (Phoenix dactylifera L.) has been known for many health benefits, but its antihyperlipidaemic activity still remains unclear. OBJECTIVE: To investigate effects of Birhi date palm fruit, “Khalal” and “Tamr, on serum lipids, body weight and food intake in cholesterol-fed rats. METHODS: Sixty male Sprague–Dawley rats were assigned into 5 cholesterol-free (control) or 5 cholesterol-supplemented (experimental) diets containing 0%, 5% and 10% of either Khalal or Tamr and given ad libitum to the rats for 6 weeks. Serum total cholesterol (TC), low- and very low-density lipoprotein cholesterol (LDL-C and VLDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were then quantified and other biological parameters were assessed. RESULTS: Compared to control, cholesterol induced significant (p < 0.05) increase in serum LDL-C, TC/TG ratio and atherogenic index and decrease in TG and HDL-C/LDL-C ratio, whereas other lipid fractions, food intake and weight gain were unchanged. In all rats, none of the studied variables were appreciably affected by dates feeding, except for increased (p < 0.05) and linearly responded (r 2 = 0.348, p < 0.01) atherogenic index induced by Khalal. Lipid variables and their calculated ratios that were increased or decreased by cholesterol remained unaffected by dates feeding. CONCLUSON: In normal or cholesterol-fed rats, Birhi Khalal or Tamr exert little or no effect on serum lipids and are ineffective to counteract the atherogenic effect of cholesterol.

Effects of cholesterol-supplemented and unsupplemented diets containing unextracted and extracted Syzygium cumini seeds on lipid profiles of alloxan-induced diabetic albino rats

Background: Hypercholesterolemia and hyperlipidemia are the major problems associated with diabetes. Various agents are being tried to solve these so that problems related to micro- and macroangiopathy can be averted. Plant fibers particularly water-soluble gummy fibers have been reported earlier to reduce blood lipids and cholesterol levels in normal and diabetic animals and humans. Objective: Effects of cholesterol-supplemented and unsupplemented diets containing unextracted and extracted Syzygium cumini seeds on lipid profiles of alloxan-induced diabetic albino rats Material and Methods: Powder of Syzygium cumini seeds was successively extracted using organic solvents, and hypolipidemic and hypocholesterolemic activities of 15% unextracted, 15% extracted, and 15% degummed S. cumini seeds with cholesterol-supplemented and unsupplemented diets were assayed in normal and alloxan-induced diabetic rats. Result: In this study, significant decrease in the levels of total serum cholesterol, serum triglycerides, serum phospholipids, and total cholesterol and triglycerides in tissues of liver, heart, and aorta was observed. Also, significant increase was observed in the phospholipid levels in tissues of liver, heart, aorta, and biliary, and fecal bile acid content and sterols in normal and alloxan-induced diabetic rats. Conclusion: The hypocholesterolemic and hypolipidemic effects of S. cumini seeds may be attributed to their watersoluble gel-forming gummy fiber acting by decreasing cholesterol absorption and breakdown leading to an increased fecal excretion of bile acids and sterols.

Effects of Aster scaber Seed Oil Containing trans-Δ3 Fatty Acids on Lipid Profiles of Hamsters and Rats.

The effects of Aster scaber seed oil (ASO) on lipid profiles were studied in rats and hamsters. ASO contained considerable amounts of Δ3t-16:1 (11.4%), Δ3t, 9c-18:2 (4.6%), and Δ3t, 9c, 12c-18:3 (11.3%). Young rats and hamsters were fed diets containing ASO, soybean oil (SBO), or olive oil (OLO) as fat sources for 4 weeks in separate experiments with or without cholesterol. In the rat study, there were no significant differences in the concentrations of serum total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triacylglycerol among the groups. The serum but not liver malondialdehyde (MDA) level was significantly lower in the ASO-fed group than it was in the other groups. The biochemical and growth parameters revealed no significant biological damages in the ASO-fed animals. In the hamster study, dietary cholesterol-dependent effects were evident in the serum lipids profiles, whereas the fat-induced effect was only observed in the ratio of serum low-density lipoprotein (LDL)-/HDL-cholesterol. Furthermore, fat- and cholesterol-induced effects were evident in the ratio of serum LDL-/HDL-cholesterol. Significant interactions between dietary fat and cholesterol were observed as evident from the concentration of serum cholesterol and triacylglycerol, as well as the activity of serum cholesterol ester transfer protein. These results suggest that dietary ASO containing trans-Δ3 fatty acids appeared to improve the serum LDL-/HDL-cholesterol ratio more than the SBO did, especially when hamsters were simultaneously fed cholesterol-supplemented diet.

Effects of Jamaican bitter yam (Dioscorea polygonoides) and diosgenin on blood and fecal cholesterol in rats.

A sapogenin-rich preparation from Jamaican bitter yam (Dioscorea polygonoides) has been shown to reduce blood cholesterol concentrations in hypercholesterolemic rats and mice. Also, diosgenin supplementation has been reported to have antilipemic effects in several animal species. We investigated potential mechanisms of the lipid-lowering actions of bitter yam and also whether the actions were mediated by diosgenin. Sprague-Dawley rats were fed a hypercholesterolemic diet (4% cholesterol) alone or with 5% bitter yam or 1% diosgenin supplementation for 6 weeks. The control group was fed normal rat chow. The serum lipid profile, fecal cholesterol concentration, and serum lipase activity were assessed at the end of the period. The induction of hypercholesterolemia was inhibited by coadministration of 5% bitter yam or 1% diosgenin in the diet. Serum lipid profiles were similar in rats fed bitter yam or diosgenin. The fecal cholesterol concentration was significantly (P < .01) higher in rats fed diosgenin compared to the cholesterol group. However, there was no corresponding elevation in the group fed bitter yam. Administration of bitter yam or diosgenin supplement significantly increased (P < .01) the serum lipase activity compared to the normal control and cholesterol groups. The cholesterol-supplemented diet inhibited normal gain in body weight over the period. This action was potentiated by diosgenin. The effects of the respective supplements on body weight were not completely explained by food consumption. Supplementation of the diet with Jamaican bitter yam may be therapeutically beneficial in the management of hypercholesterolemia.

Rapid Development of Non-Alcoholic Steatohepatitis in Psammomys obesus (Israeli Sand Rat)

Background and AimsA major impediment to establishing new treatments for non-alcoholic steatohepatitis is the lack of suitable animal models that accurately mimic the biochemical and metabolic characteristics of the disease. The aim of this study was to explore a unique polygenic animal model of metabolic disease as a model of non-alcoholic steatohepatitis by determining the effects of 2% dietary cholesterol supplementation on metabolic and liver endpoints in Psammomys obesus (Israeli sand rat).Methods P. obesus were provided ad libitum access to either a standard rodent diet (20% kcal/fat) or a standard rodent diet supplemented with 2% cholesterol (w/w) for 4 weeks. Histological sections of liver from animals on both diets were examined for key features of non-alcoholic steatohepatitis. The expression levels of key genes involved in hepatic lipid metabolism were measured by real-time PCR.Results P. obesus fed a cholesterol-supplemented diet exhibited profound hepatomegaly and steatosis, and higher plasma transaminase levels. Histological analysis identified extensive steatosis, inflammation, hepatocyte injury and fibrosis. Hepatic gene expression profiling revealed decreased expression of genes involved in delivery and uptake of lipids, and fatty acid and triglyceride synthesis, and increased expression of genes involved in very low density lipoprotein cholesterol synthesis, triglyceride and cholesterol export.Conclusions P. obesus rapidly develop non-alcoholic steatohepatitis when fed a cholesterol-supplemented diet that appears to be histologically and mechanistically similar to patients.

A Dietary Test of Putative Deleterious Sterols for the Aphid Myzus persicae

The aphid Myzus persicae displays high mortality on tobacco plants bearing a transgene which results in the accumulation of the ketosteroids cholestan-3-one and cholest-4-en-3-one in the phloem sap. To test whether the ketosteroids are the basis of the plant resistance to the aphids, M. persicae were reared on chemically-defined diets with different steroid contents at 0.1–10 µg ml−1. Relative to sterol-free diet and dietary supplements of the two ketosteroids and two phytosterols, dietary cholesterol significantly extended aphid lifespan and increased fecundity at one or more dietary concentrations tested. Median lifespan was 50% lower on the diet supplemented with cholest-4-en-3-one than on the cholesterol-supplemented diet. Aphid feeding rate did not vary significantly across the treatments, indicative of no anti-feedant effect of any sterol/steroid. Aphids reared on diets containing equal amounts of cholesterol and cholest-4-en-3-one showed fecundity equivalent to aphids on diets containing only cholesterol. Aphids were reared on diets that reproduced the relative steroid abundance in the phloem sap of the control and modified tobacco plants, and their performance on the two diet formulations was broadly equivalent. We conclude that, at the concentrations tested, plant ketosteroids support weaker aphid performance than cholesterol, but do not cause acute toxicity to the aphids. In plants, the ketosteroids may act synergistically with plant factors absent from artificial diets but are unlikely to be solely responsible for resistance of modified tobacco plants.

Effects of selective inhibition of reverse mode of Na(+)/Ca(2+) exchanger on rats with contrast-induced acute kidney injury

Intracellular Ca(2+) overload is a key factor in contrast-induced renal tubular toxicity. Na(+)/Ca(2+) exchanger (NCX) system is one of main pathways of intracellular Ca(2+) overload. We explore the effects of KB-R7943, an inhibitor of reverse mode of NCX, on contrast-induced acute kidney injury (CI-AKI). Rats were divided into control, CI-AKI and pre-treatment groups with KB-R7943 (5, 10 mg/kg). CI-AKI was induced by diatrizoate administration in rats with cholesterol-supplemented diet for 8 weeks. Renal function and hemodynamics were determined at Day 1 post-administration. Renal histopathology was observed under light microscope. Renal tubular apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Renal endothelin-1 (ET-1) was measured by radioimmunoassay. The oxidative markers of renal malondialdehyde (MDA) and catalase (CAT) were measured. The expression of NCX was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Levels of serum creatinine (Scr, µmol/L ) in CI-AKI rats ((149 ± 35) µmol/L) were significantly higher than those of normal rats ((55 ± 4) µmol/L, P < 0.01). Renal ET-1, MDA and CAT, resistance index (RI) of renal blood vessels increased significantly in CI-AKI rats. The contrast-induced increases in Scr and RI of renal blood vessels were suppressed significantly and dose-dependently by pretreatment with KB-R7943. Histopathological and TUNEL results showed that contrast-induced severe renal tubular necrosis and apoptosis were significantly and dose-dependently attenuated by KB-R7943. KB-R7943 significantly suppressed the contrast-induced increments of ET-1, MDA and CAT. No significant changes in NCX1 mRNA expression were observed following contrast administration. Renal oxidative stress and ET-1 overproduction via the activation of reverse mode of NCX play an important role in the pathogenesis of CI-AKI. And inhibition of reverse mode of NCX expressed in renal tubular epithelial cell has protective effects on CI-AKI.

Effects of dietary flaxseed on atherosclerotic plaque regression

Dietary flaxseed can retard the progression of atherosclerotic plaques. However, it remains unclear whether these antiatherogenic effects extend to plaque regression. In the present study, the therapeutic potential of dietary flaxseed on atherosclerotic plaque regression and vascular contractile function was evaluated using a novel rabbit model. Rabbits were randomly assigned to receive either a regular diet for 12 wk (group I) or a 1% cholesterol-supplemented diet for 4 wk followed by a regular diet for 8 wk (group II). The remaining experimental animals were treated as in group II but were fed for an additional 14 wk with either a regular diet (group III) or a 10% flaxseed-supplemented diet (group IV). Animals in group II showed clear evidence of plaque growth stabilization. Their vessels also exhibited significantly lower norepinephrine-induced contraction and an impaired relaxation response to acetylcholine compared with animals in group I. Dietary flaxseed supplementation resulted in a significant ≈40% reduction in plaque formation (P = 0.033). Animals in both groups II and III displayed improved contraction and endothelium-dependent vessel relaxation. Dietary flaxseed is a valuable strategy to accelerate the regression of atherosclerotic plaques; however, flaxseed intervention did not demonstrate a clear beneficial effect on the vessel contractile response and endothelium-dependent vasorelaxation.

Na+/Ca2+ exchange inhibitor, KB-R7943, attenuates contrast-induced acute kidney injury

Intracellular Ca2+ overload is considered to be a key factor in contrast-induced acute kidney injury (CI-AKI). The Na+/Ca2+ exchanger (NCX) system is one of the main pathways of intracellular Ca2+ overload. We investigated the effects of KB-R7943, an inhibitor of the reverse mode of NCX, on CI-AKI in a rat model. Rats were divided into control group, CI-AKI group and pretreatment groups (with KB-R7943 dose of 5 or 10 mg/kg). CI-AKI was induced by diatrizoate administration in rats with cholesterol-supplemented diet for 8 weeks. Renal function and renal hemodynamics were determined 1 day following contrast medium administration. Renal histopathology was observed by light microscope. Renal tubular apoptosis was examined by TUNEL. Renal endothelin-1 (ET-1) was measured by radioimmunoassay. Renal malondialdehyde (MDA) and catalase (CAT) were measured as oxidative markers. Levels of serum creatinine (Scr), renal ET-1, MDA and CAT, and resistance index (RI) of renal blood vessels increased significantly in CI-AKI rats. The increases in Scr and RI of renal blood vessels induced by diatrizoate were suppressed significantly and dose-dependently by pretreatment with KB-R7943. Histopathological and TUNEL results showed that the contrast medium-induced severe renal tubular necrosis and apoptosis were significantly and dose-dependently attenuated by KB-R7943. KB-R7943 significantly suppressed the increment of renal ET-1 content and MDA and CAT level induced by contrast medium administration. Activation of the reverse mode of NCX, followed by ET-1 overproduction and increased oxidative stress, seems to play an important role in the pathogenesis of CI-AKI. The inhibitor of the reverse mode of NCX, KB-R7943, has renoprotective effects on CI-AKI.

Probucol prevents blood–brain barrier dysfunction in wild‐type mice induced by saturated fat or cholesterol feeding

Dysfunction of the blood-brain barrier (BBB) is an early pathological feature of vascular dementia and Alzheimer's disease (AD) and is triggered by inflammatory stimuli. Probucol is a lipid-lowering agent with potent anti-oxidant properties once commonly used for the treatment of cardiovascular disease. Probucol therapy was found to stabilize cognitive symptoms in elderly AD patients, whereas in amyloid transgenic mice probucol was shown to attenuate amyloidosis. However, the mechanisms underlying the effects of probucol have note been determined. In the present study we investigated whether probucol can prevent BBB disturbances induced by chronic ingestion of proinflammatory diets enriched with either 20% (w/w) saturated fats (SFA) or 1% (w/w) cholesterol. Mice were fed the diets for 12 weeks before they were killed and BBB integrity was measured. Mice maintained on either the SFA- or cholesterol-supplemented diets were found to have a 30- and sevenfold greater likelihood of BBB dysfunction, respectively, as determined by the parenchymal extravasation of plasma-derived immunoglobulins and endogenous lipoprotein enrichment with β-amyloid. In contrast, mice fed the SFA- or cholesterol-enriched diets that also contained 1% (w/w) probucol showed no evidence of BBB disturbance. The parenchymal expression of glial fibrillary acidic protein, a marker of cerebrovascular inflammation, was significantly greater in mice fed the SFA-enriched diet. Plasma lipid, β-amyloid and apolipoprotein B levels were not increased by feeding of the SFA- or cholesterol-enriched diets. However, mice fed the SFA- or cholesterol-enriched diets did exhibit increased plasma non-esterified fatty acid levels that were not reduced by probucol. The data suggest that probucol prevents disturbances of BBB induced by chronic ingestion of diets enriched in SFA or cholesterol by suppressing inflammatory pathways rather than by modulating plasma lipid homeostasis.