Reduced Plasma Cholesterol Levels Research Articles

Effects of dietary plant meal and soya-saponin supplementation on intestinal and hepatic lipid droplet accumulation and lipoprotein and sterol metabolism in Atlantic salmon (Salmo salarL.)

Altered lipid metabolism has been shown in fish fed plant protein sources. The present study aimed to gain further insights into how intestinal and hepatic lipid absorption and metabolism are modulated by plant meal (PM) and soya-saponin (SA) inclusion in salmon feed. Post-smolt Atlantic salmon were fed for 10 weeks one of four diets based on fishmeal or PM, with or without 10 g/kg SA. PM inclusion resulted in decreased growth performance, excessive lipid droplet accumulation in the pyloric caeca and liver, and reduced plasma cholesterol levels. Intestinal and hepatic gene expression profiling revealed an up-regulation of the expression of genes involved in lipid absorption and lipoprotein (LP) synthesis (apo, fatty acid transporters, microsomal TAG transfer protein, acyl-CoA cholesterol acyltransferase, choline kinase and choline-phosphate cytidylyltransferase A), cholesterol synthesis (3-hydroxy-3-methylglutaryl-CoA reductase) and associated transcription factors (sterol regulatory element-binding protein 2 and PPARγ). SA inclusion resulted in reduced body pools of cholesterol and bile salts. The hepatic gene expression of the rate-limiting enzyme in bile acid biosynthesis (cytochrome P450 7A1 (cyp7a1)) as well as the transcription factor liver X receptor and the bile acid transporter abcb11 (ATP-binding cassette B11) was down-regulated by SA inclusion. A significant interaction was observed between PM inclusion and SA inclusion for plasma cholesterol levels. In conclusion, gene expression profiling suggested that the capacity for LP assembly and cholesterol synthesis was up-regulated by PM exposure, probably as a compensatory mechanism for excessive lipid droplet accumulation and reduced plasma cholesterol levels. SA inclusion had hypocholesterolaemic effects on Atlantic salmon, accompanied by decreased bile salt metabolism.

Electrochemical oxidation behavior of ezetimibe and its adsorptive stripping determination in pharmaceutical dosage forms and biological fluids

Ezetimibe (EZE) is a drug that reduces plasma cholesterol levels and performs by decreasing cholesterol absorption in intestines. In this study, we examined the electrochemical behavior of EZE on a glassy carbon electrode and optimum conditions for its quantitative determination by using voltammetric methods. In addition, some electrochemical parameters such as diffusion coefficient, surface coverage of adsorbed molecules, electron transfer coefficient, standard rate constant and number of electrons were calculated by using the results of cyclic voltammetry. A tentative mechanism for the oxidation for EZE is suggested. As a result of bulk electrolysis and cyclic voltammetric experiments, an intermediate product occurred. The oxidation signal of the EZE molecule was used to develop fully validated, new, rapid, selective and simple square-wave anodic adsorptive stripping voltammetric (AdsSWV) and differential pulse anodic stripping voltammetric (AdsDPV) methods to direct determination of EZE in pharmaceutical dosage forms and biological samples. As a result of these studies, for the AdsDPV and AdsSWV techniques, linear working ranges were found to be 4.0 × 10−7–7.6 × 10−6 and 4.0 × 10−7–6.0 × 10−6 mol L−1, respectively. The detection limits obtained from AdsDPV and AdsSWV were calculated to be 1.529 × 10−7 and 1.185 × 10−7mol L−1, respectively. Moreover, the limit of quantification was evaluated for AdsDPV and AdsSWV methods and found to be 5.098 × 10−7 and 3.951 × 10−7 mol L−1, respectively. The developed methods for EZE were successfully applied to assay the drug in tablets, human blood serum and human urine.

Recent progress in the development of apoA–I and apoE mimetic therapies

Historical perspectives Epidemiological studies demonstrate a clear inverse association of HDL with cardiovascular disease. Results from the Framingham Heart Study demonstrate that low levels of HDL are an independent risk factor for coronary heart disease (CHD). Statins, which can reduce levels of apoB-containing lipoproteins and plasma cholesterol levels, have been only partially successful at reducing the risk of CHD, while 70% of the problem remains to be solved. In addition, with the increasing prevalence of metabolic syndrome, in order to successfully address the prevailing CHD problem, there is a need for an alternate mode of therapy than simply to reduce plasma cholesterol levels. Thus, much recent attention has focused on studying HDL as an alternate therapy. Badimon et al. showed that administering human HDL to cholesterol-fed rabbits regressed atherosclerotic plaque formation [1]. Since apoA-I is the major protein component of HDL, studies with isolated apoA-I in the presence of lipid have been performed [2], termed recombinant HDL therapy. Transgenic expression of human apoA-I in athero sclerosis-sensitive mouse models also demonstrated significant inhibition of atherosclerosis [3]. The field got a boost when apoA-I milano –lipid complexes (40 mg/kg of protein) were infused in humans and the results were followed by intravenous ultrasound. When apoA-I milano –POPC complexes were infused in 40 patients, there was a significant decrease in the atheroma volume (between 3.5 and 5%) compared with baseline as studied by intravenous ultrasound [4]. However, perhaps due to the prohibitive cost of producing human or recombinant apoA-I, this technology has not

The Benefits of Sequestration

Biomedicine About 170 million people worldwide are infected with hepatitis virus (HCV), which causes progressive liver disease, and current antiviral therapies are only partially effective and/or cause adverse side effects. HCV survival and replication require binding of the viral genomic RNA to a noncoding RNA of host origin that is abundant in the liver, called miR-122. Therapies that lower miR-122 levels have been tested in preclinical models of HCV infection with encouraging results. Janssen et al. now report the results of a phase 2a clinical trial designed to assess the safety and efficacy of a chemically modified antisense oligonucleotide that sequesters miR-122 into a stable heteroduplex, thereby inhibiting its function. In a study of 27 HCV-infected patients receiving five weekly injections of the oligonucleotide, those receiving the highest dose showed a substantial decline in plasma HCV levels that persisted for about 15 weeks before rebounding. No significant side effects were observed and, as a bonus, a 25% reduction in plasma cholesterol levels was observed. N. Engl. J. Med. 368 , 1685 (2013).

Evidence of health benefits of canola oil

Canola oil-based diets have been shown to reduce plasma cholesterol levels in comparison with diets containing higher levels of saturated fatty acids. Consumption of canola oil also influences biological functions that affect various other biomarkers of disease risk. Previous reviews have focused on the health effects of individual components of canola oil. Here, the objective is to address the health effects of intact canola oil, as this has immediate practical implications for consumers, nutritionists, and others deciding which oil to consume or recommend. A literature search was conducted to examine the effects of canola oil consumption on coronary heart disease, insulin sensitivity, lipid peroxidation, inflammation, energy metabolism, and cancer cell growth. Data reveal substantial reductions in total cholesterol and low-density lipoprotein cholesterol, as well as other positive actions, including increased tocopherol levels and improved insulin sensitivity, compared with consumption of other dietary fat sources. In summary, growing scientific evidence supports the use of canola oil, beyond its beneficial actions on circulating lipid levels, as a health-promoting component of the diet.

New targets and developments in lipoproteins control

New targets and developments in lipoproteins control Giuseppe Danilo Norata1–31Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy; 2Center for the Study of Atherosclerosis, Società Italiana Studio Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy; 3The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UKAbstract: Statins provide a very effective approach in reducing plasma cholesterol levels and cardiovascular risk. However, the proportion of patients who fail to achieve desirable plasma lipid levels ranges from 16%–53%, worldwide. This percentage reaches up to 80% in patients with familial hypercholesterolemia. Additionally, many patients are unable to tolerate statins, particularly at the highest approved dose level. New treatments that aggressively reduce lipid levels in patients with severe hypercholesterolemia, or those unable to reach their lipid targets, are therefore required. The most promising approaches in this context, such as inhibitors of the synthesis of apolipoprotein B (apoB) containing lipoproteins (apoB silencing or microsomal triglyceride transfer protein [MTP] inhibition) or proprotein convertase subtilisin/kexin type 9 (PCSK9) blockers, all decrease low-density lipoprotein (LDL) extensively. Increasing low levels of high-density lipoprotein (HDL) cholesterol via cholesteryl ester transfer protein inhibitors or apolipoprotein A-1 (ApoA-1) inducers and improving their quality with HDL or ApoA-1 mimetics represent also important options. Drugs affecting HDL, however, may not be all alike and require adequate scrutiny of the mechanisms involved. Until we have a better understanding of these issues, further LDL lowering in high-risk patients represents the soundest approach.Keywords: apolipoproteins, lipids, lipoprotein classes, hypercholesterolemia, synthesis, LDL lowering

Effect of Potato Ethanol Residue on Rat Plasma Cholesterol Levels

We investigated the cholesterol-lowering effect of a potato ethanol residue (PER). The plasma cholesterol levels excluding high-density lipoprotein cholesterol were lower in the rats given a PER-containing diet for 6 weeks than in the control group, whereas the fecal cholesterol levels were higher. These results suggest that PER partially reduced plasma cholesterol levels via excretion of cholesterol into the feces.

Bile acid sequestration normalizes plasma cholesterol and reduces atherosclerosis in hypercholesterolemic mice. No additional effect of physical activity

AimsBile acid sequestrants (BAS) and physical activity (RUN) decrease incidence of cardiovascular events. Both treatments are often prescribed, yet it is not known whether their beneficial effects are additive. We assessed the effects of BAS treatment alone and in combination with RUN on cholesterol metabolism, heart function and atherosclerotic lesion size in hypercholesterolemic mice. MethodsMale Ldlr-deficient mice remained either sedentary (CONTROL), were treated with Colesevelam HCl (BAS), had access to a running wheel (RUN), or were exposed to BAS and RUN (BAS RUN). All groups were fed a high cholesterol diet for 12 weeks. Then, feces, bile and plasma were collected. Atherosclerotic lesion size was determined in the aortic arch and heart function by echocardiography. ResultsBAS RUN ran more than RUN (6.4 ± 1.4 vs. 3.5 ± 1.0 km/day, p < 0.05). BAS and BAS RUN displayed ∼3-fold reductions in plasma cholesterol levels (p < 0.001), ∼2.5-fold increases in fecal neutral sterol (p < 0.001) and bile acid (p = 0.01) outputs, decreases in biliary secretions of cholesterol (∼6-fold, p < 0.0001) and bile acids (∼2-fold, p < 0.001) vs. CONTROL while no significant effects were observed in RUN. Compared to CONTROL, lesion size decreased by 78% in both BAS and BAS RUN, (p < 0.0001). ConclusionBAS reduce atherosclerosis in Ldlr-deficient mice, coinciding with a switch from body cholesterol accumulation to cholesterol loss. RUN slightly modulated atherosclerotic lesion formation but the combination of BAS and RUN had no clear additive effects in this respect.

Reducing plasma cholesterol is not the end of the quest

Despite the cholesterol lowering beneficial effects of statins, nearly 70% of cardiovascular disease remains unresolved. High density lipoproteins (HDL), apolipoprotein A-I (the major protein component of HDL), and apoA-I mimetic peptides exert antiinflammatory effects but have not been shown to reduce plasma cholesterol levels. Apolipoprotein E (apoE) is a protein component of chylomicron remnants, very low density lipoprotein (VLDL), and HDL. ApoE is ubiquitously expressed and secreted by many tissues in the body including liver, brain, skin, and tissue macrophages [1]. A common well-characterized polymorphism in human apoE gene accounts for the three alleles, e2, e 3a nde4 that are known to confer resistance or susceptibilitytomany diseasesincludingAlzheimer’sdisease[2]and atherosclerosis [3]. ApoE gene encodes for a 299 amino acid protein containing two domains: a receptor-binding domain at the N-ter

New compounds able to control hepatic cholesterol metabolism: Is it possible to avoid statin treatment in aged people?

Aging is characterized by the loss of homeostasis that leads to changes in the biochemical composition of tissues, reduced ability to respond adaptively to environmental stimuli, and increased susceptibility and vulnerability to diseases including coronary artery diseases, carotid artery disease and brain vessel disease. Hypercholesterolemia is one of the primary risk factors for these pathologies, whose incidence is highly related to aging. Almost 25% of men and 42% of women older than 65 years have a serum total cholesterol level greater than 240 mg/dL. The mechanisms behind this age-related increase in plasma cholesterol are still incompletely understood, thus, the control of plasma cholesterol content in aged people is more challenging than in adults. In this review the different pharmacological approaches to reduce plasma cholesterol levels, particularly in aged people, will be discussed. In brief, current therapies are mostly based on the prescription of statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) that are pretty effective but that exert several side effects. More attention should be given to potential drug interactions, potential age-related changes in drug pharmacokinetics, adverse effects such as myopathy and competing risks when statins are prescribed to old patients. In combination or in alternative to statin therapy, other agents might be required to reduce low density lipoprotein (LDL) cholesterol levels. Among the available drugs, the most commonly prescribed are those addressed to reduce cholesterol absorption, to modulate lipoprotein lipase activity and bile acid sequestrants: even these pharmacological interventions are not exempt from side effects. The use of antioxidants or organoselenium compounds and the discovery of new proteins able to modulate exclusively LDL receptor recycling such as Proprotein convertase subtilisin kexin 9 and SEC24 offer new pharmacological approaches to selectively reduce the main causes of dyslipidemia.

Two apolipoprotein E mimetic peptides with similar cholesterol reducing properties exhibit differential atheroprotective effects in LDL-R null mice

ObjectiveWe investigated two apoE mimetic peptides with similar long-term plasma cholesterol reducing abilities for their effects on atherosclerotic lesions in Western diet-fed female LDL-receptor (LDL-R) null mice. Methods and resultsSingle doses of peptides Ac-hE18A-NH2 and mR18L were administered retro-orbitally to LDL-R null mice on Western diet and plasma cholesterol was measured at 10 min, 4 h, and 24 h post administration. Peptide mR18L and not Ac-hE18A-NH2 reduced plasma cholesterol levels significantly at 4 h post administration. However, multiple administrations (100 μg/mouse twice weekly for 8 weeks) resulted in a similar reduction in plasma cholesterol. Only the plasma from the Ac-hE18A-NH2 group had significantly reduced reactive oxygen species levels at the end of the treatment protocol. Both mR18L and Ac-hE18A-NH2 showed reduced atherosclerotic lesion areas. However, peptide Ac-hE18A-NH2 was significantly more effective in inhibiting atherosclerosis. Both peptides reduced total plaque macrophage load compared to the saline treated animals, with peptide Ac-hE18A-NH2 having a greater reduction. Incubation of HepG2 cells and THP-1 monocyte-derived macrophages with both peptides in the presence of oxidized phospholipid showed that Ac-hE18A-NH2 promotes the secretion of apoE from the cells whereas mR18L does not. ConclusionsDespite similar reductions in plasma cholesterol levels, Ac-hE18A-NH2 was more effective in inhibiting lesions than mR18L, possibly due to its ability to promote the secretion of apoE from hepatocytes and macrophages.

New Clinical Perspectives of Hypolipidemic Drug Therapy in Severe Hypercholesterolemia

Patients with homozygous familial hypercholesterolemia (HoFH) represent the most severe patients within the spectrum of dyslipidemias. Untreated Low-Density Lipoprotein Cholesterol (LDL-C) levels in these patients are usually in the range 500 to 1200 mg/dL. Moreover, these patients exhibit a scarce responsiveness or even non responsiveness to oral lipid lowering agents. Patients with heterozygous familial hypercholesterolemia (HetFH) tend to have untreated LDL-C levels of 250-500 mg/dL. Many of these patients are responsive to 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA-reductase) inhibitors (statins) and/or other specific drugs. Unfortunately, a significant subset of these patients (5-10%) have a severe and/or refractory form of HetFH and after current maximal oral therapy, they remain significantly far from treatment goals (The National Cholesterol Education Program (NCEP) ATPIII guidelines). This would be defined as LDL-C levels of ≥ 190 mg/dL - prior Coronary Heart Disease (CHD) or CHD equivalent - or ≥ 250 mg/dL (no prior CHD or CHD risk-equivalent). The only current therapy option for these patients is Low Density Lipoprotein-apheresis (LDL_a). While LDL_a is very effective in reducing LDL-C, many patients do not receive this extracorporeal therapy because of costs and limited availability of LDL_a centers. Recently, new potent lipid-lowering drugs have been developed and are currently under investigation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role controlling the levels of LDL-C. Studies have demonstrated that PCSK9 acts mainly by enhancing degradation of the Low-Density Lipoprotein receptor (LDLR) protein in the liver. Inactivation of PCSK9 in mice reduces plasma cholesterol levels. Since the loss of a functional PCSK9 in human is not associated with apparent deleterious effects, this protease is becoming an attractive target for lowering plasma LDL-C levels either alone or in combination with statins. Mipomersen, an apolipoprotein B (ApoB) synthesis inhibitor, for lowering of LDL-C showed to be an effective therapy to reduce LDL-C concentrations in patients with HoFH who are already receiving lipid-lowering drugs, including high-dose statins. Lomitapide is a potent inhibitor of microsomal triglyceride transfer protein and is highly efficacious in reducing LDL-C and triglycerides (TG). Lomitapide is currently being developed for patients with HoFH at doses up to 60 mg/d. These new powerful lipid-lowering drugs might be possibly superior than available hypolipidemic agents. Their mechanisms of action, effectiveness, safety, and indication in severe, genetically determined dyslipidemias, are reviewed.

Discovery of novel indane derivatives as liver-selective thyroid hormone receptor β (TRβ) agonists for the treatment of dyslipidemia

Thyromimetics that specifically target TRβ have been shown to reduce plasma cholesterol levels and avoid atherosclerosis through the promotion of reverse cholesterol transport in an animal model. We designed novel thyromimetics with high receptor (TRβ) and organ (liver) selectivity based on the structure of eprotirome (3) and molecular modeling. We found that indane derivatives are potent and dual-selective thyromimetics expected to avoid hypothyroidism in some tissues as well as heart toxicity. KTA-439 (29), a representative indane derivative, showed the same high human TRβ selectivity in a binding assay as 3 and higher liver selectivity than 3 in a cholesterol-fed rat model.

Effects of PKF275-055, a dipeptidyl peptidase–4 inhibitor, on the development of atherosclerotic lesions in apolipoprotein E–null mice

We recently discovered that glucagon-like peptide–1 and glucose-dependent insulinotropic polypeptide can both prevent the development of atherosclerosis in apolipoprotein E–null (Apoe−/−) mice. In the present study, we attempted to extend these findings to orally administered dipeptidyl peptidase (DPP)–4 inhibitor. Seventeen-week-old Apoe−/− mice fed an atherogenic diet were administered a DPP-4 inhibitor, vildagliptin analogue (PKF275-055 [PKF], 100 µm/[kg d]), in drinking water over a period of 4 weeks. Aortic atherosclerosis and oxidized low-density lipoprotein–induced foam cell formation were determined. Orally administered PKF increased plasma levels of active glucagon-like peptide–1 by 3.5-fold, increased total glucose-dependent insulinotropic polypeptide levels by 2-fold, reduced body weight by 13%, and reduced plasma cholesterol levels by 30%. Compared with drinking water controls, PKF significantly suppressed total aortic atherosclerotic lesions, atheromatous plaque in the aortic root, and macrophage accumulation in the aortic wall by 30% to 40% (P < .001). None of these changes were associated with the PKF-induced reductions in body weight and plasma cholesterol levels. Foam cell formation was suppressed by 40% in the exudate peritoneal macrophages obtained from the PKF-treated mice. The DPP-4 inhibitor prevents the development of atherosclerotic lesions by suppressing macrophage foam cell formation.

Apolipoprotein E Mimetics and Cholesterol-Lowering Properties

Apolipoprotein E (apoE) is a ligand for clearance of lipoprotein remnants such as chylomicrons and very low-density lipoproteins. It has anti-atherogenic and anti-inflammatory properties. Therefore, there is extensive ongoing research to create peptides that can mimic properties of apoE. A number of synthetic peptides that encompass different regions of apoE have been studied for inhibiting inflammatory states, including Alzheimer disease. However, peptides that clear atherogenic lipoproteins, analogous to apoE, via enhanced hepatic uptake have not been previously reviewed. Toward this end, we describe the design and studies of a dual-domain apoE mimetic peptide, Ac-hE18A-NH(2). This peptide consists of residues 141-150, the putative receptor-binding region of human apoE, covalently linked to a well characterized class A amphipathic helix, 18A, which has no sequence homology to any other exchangeable apolipoprotein sequences. It demonstrates dramatic effects in reducing plasma cholesterol levels in dyslipidemic mouse and rabbit models. We discuss the scientific rationale and review the literature for the design and efficacy of the peptide. Analogous to apoE, this peptide bypasses the low-density lipoprotein receptor for the hepatic uptake of atherogenic lipoproteins via heparan sulfate proteoglycan (HSPG). ApoE mimetics such as Ac-hE18A-NH(2) may therefore restore or replace ligands in genetically induced hyperlipidemias to enable reduction in atherogenic lipoproteins via HSPG even in the absence of functional low-density lipoprotein receptors. Therefore, this and similar peptides may be useful in the treatment of dyslipidemic disorders such as familial hyperlipidemia and atherosclerosis.

Reduced cholesterol and triglycerides in mice with a mutation in Mia2, a liver protein that localizes to ER exit sites

Through forward genetic screening in the mouse, a recessive mutation (couch potato, cpto) has been discovered that dramatically reduces plasma cholesterol levels across all lipoprotein classes. The cpto mutation altered a highly conserved residue in the Src homology domain 3 (SH3) domain of the Mia2 protein. Full-length hepatic Mia2 structurally and functionally resembled the related Mia3 protein. Mia2 localized to endoplasmic reticulum (ER) exit sites, suggesting a role in guiding proteins from the ER to the Golgi. Similarly to the Mia3 protein, Mia2's cytosolic C terminus interacted directly with COPII proteins Sec23 and Sec24, whereas its lumenal SH3 domain may facilitate interactions with secretory cargo. Fractionation of plasma revealed that Mia2(cpto/cpto) mice had lower circulating VLDL, LDL, HDL, and triglycerides. Mia2 is thus a novel, hepatic, ER-to-Golgi trafficking protein that regulates cholesterol metabolism.

Relationship Between Cholesterol Metabolism, Apoe and Brain Volumes In Alzheimer‘s Disease

APOE genotype, aging and midlife hypercholesterolemia are well-established risk factors for late-onset Alzheimer’s disease (AD). ApoE and cholesterol are involved in the pathogenesis of AD since they influence amyloid-β accumulation and Tau pathology. APOE ε4 carriers were found to present lower levels of amyloid-β1–42, higher tau and phosphorylated tau and a higher degree of brain atrophy at any disease stage. Presence of ApoE4 shifts the onset of the disease towards a younger age and makes progression faster. Hypercholesterolemia together with other major cardiovascular risk factors were found to be involved in the pathogenesis of AD, but reduced plasma cholesterol levels were described in demented patients. Significant correlations were found between cholesterol precursors lathosterol, lanosterol and 24S-hydroxycholesterol (a putative marker of brain cholesterol turnover) in plasma and brain atrophy as quantified by MRI. It is likely that neurodegeneration affects both brain and whole-body cholesterol metabolism in AD.

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9% and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15%), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3% and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3%) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.

Beyond cholesterol-lowering effects of plant sterols: clinical and experimental evidence of anti-inflammatory properties

Inflammation is a strong risk factor for cardiovascular disease. Dietary plant sterols are known to reduce plasma cholesterol levels and thereby reduce cardiovascular risk. Recent observations from animal and human studies have demonstrated anti-inflammatory effects of phytosterols. For example, several animal and human studies report reductions in the levels of proinflammatory cytokines, including C-reactive protein, after consumption of dietary plant sterols. Although the cholesterol-lowering effects of phytosterols in humans are well documented, studies on the effects of phytosterols on inflammatory markers have produced inconsistent results. This review summarizes and discusses findings from recent animal and human studies with regard to the potential anti-inflammatory effects of dietary phytosterols. Findings on the effects of plant sterols on inflammation remain limited and confounding. Future research using better-designed and well-controlled laboratory studies and clinical trials are needed to fully understand the mechanisms through which phytosterols influence inflammation. Additional well-designed placebo-controlled studies are needed to better understand how and to what extent dietary plant sterols may modify the immune system and the production of inflammatory markers.

Lipid Profile of Broilers Fed Zinc Bacitracin on Plant and Animal Protein Diets

This investigation was undertaken to determine the effect of protein sources and growth promoter Zinc bacitracin on the lipid profile of broiler chickens. Two trials were conducted, comprising of 240 day-old chicks and 120 day-old chicks respectively, they were housed in battery cages in a broiler pen, randomly distributed into four (4) major groups each receiving diets with protein derived from plant or animal protein with or without the addition of Zinc bacitracin. The plant and animal diets were compiled, milled and analysed, before been subdivided into two subgroups with Zinc bacitracin included at 300 g per tonne. The feeding trial lasted for six (6) weeks. On terminating the feeding trial, 30 marked birds from each group were slaughtered and blood samples were analysed for, total cholesterol, triglyceride, HDL and LDL. There was a significant difference (p<0.05) in the broiler plasma cholesterol levels, as observed in total cholesterol, HDL and LDL cholesterol levels while there was no significant difference in the triglyceride levels. Animal protein diet induced the highest cholesterol levels but on addition of Zinc bacitracin the level was reduced, as was also the case in plant diets. Reduction of plasma cholesterol levels on the inclusion of Zinc bacitracin could indicate that cholesterol is been deposited in the tissues.