Effect of X-ray radiation on the nanomechanical properties of the erythrocyte surface of rats on a high-cholesterol diet

Objective. To reveal changes in the structural and nanomechanical properties of the erythrocyte surface caused by the action of X-ray radiation in vitro on the whole blood of rats on a high-cholesterol diet using the method of atomic-force microscopy.Materials and methods. The blood of male Wistar rats being on a high-cholesterol diet for two months was exposed to X-ray radiation (320 kV) at doses of 1 and 100 Gy. The structural, elastic and adhesive properties of the surface of isolated and glutaraldehyde-fxed erythrocytes at the nanoscale were studied using the atomic- force microscope BioScope Resolve in PeakForce QNM mode in air.Results. The study has identifed an increase in the stiffness of the erythrocyte surface at a dose of 1 Gy and its decrease to almost control values at a dose of 100 Gy, which was accompanied by an increase in the size of the average cell of the erythrocyte membrane skeleton. At the same time, no signifcant changes in the morphology, adhesive properties and roughness of the relief of erythrocytes have been found.Conclusion. The obtained data indicate that X-ray radiation (1–100 Gy) induces the dose-depending reorganization of the structure and changes in the stiffness of the erythrocyte surface layer at the nanoscale without changing the cell morphology for rats on a high-cholesterol diet.

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Abstract 130: Hypercholesterolemia Suppresses Carotid Artery Endothelial NOS3 Expression via Epigenetic Mechanisms

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.130 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Alex Sotolongo ◽

Yi-Zhou Jiang ◽

John Karanian ◽

William Pritchard ◽

Peter Davies

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Endothelial Cells ◽

Dna Methyltransferase ◽

Control Group ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

High Cholesterol ◽

High Fat

Objective: One of the first clinically detectable changes in the vasculature during atherogenesis is the accumulation of cholesterol within the vessel wall. Hypercholesterolemia is characterized by dysfunctional endothelial-dependent vessel relaxation and impaired NOS3 function. Since DNA methylation at gene promoter regions strongly suppresses gene expression, we postulated that high-fat/high-cholesterol diet suppresses endothelial NOS3 through promoter DNA methylation. Methods: Domestic male pigs were fed control diet (CD) or isocaloric high fat and high cholesterol diet (HC; 12% fat and 1.5% cholesterol) for 2, 4, 8 or 12 weeks prior to tissue collection. Furthermore, to determine the effects of risk factor withdrawal, an additional group of swine received HC for 12 weeks and then CD for 8 weeks; a control group received HC continuously for 20 weeks. Endothelial cells were harvested from common carotid aorta. In parallel in vitro studies, cultured human aortic endothelial cells (HAEC) were treated with human LDL, GW3956 (LXR agonist) and RG108 (DNA methyltransferase [DNMT] inhibitor). In cells from both sources, DNA methylation at the NOS3 promoter was measured using methylation specific pyro sequencing, and endothelial gene expression was measured using RT PCR. Results: HC diet increased plasma cholesterol level from 75 mg/dl on CD to a plateau of about 540 mg/dl within 2 weeks. Endothelial NOS3 expression was significantly reduced (71±9 % of CD) after 4 weeks of HC, a level sustained at subsequent time points. Withdrawal of HC for 8 weeks did not recover NOS3 expression. After 12-week HC, the NOS3 promoter was hypermethylated. Withdrawal of HC did not reverse NOS3 promoter methylation. In vitro treatment of HAEC with human LDL (200 mg/dl total cholesterol) or GW3956 (5μM) suppressed NOS3 mRNA to 50% and 30% respectively, suggesting that LXR/RXR is involved in suppression of NOS3. Nitric oxide production was consistently suppressed by GW3959. Both could be reversed through inhibition of DNMTs by RG108. Conclusions: DNA methylation and LXR/RXR pathway can mediate the HC-suppression of endothelial NOS3. The study identifies novel pharmaceutical targets in treating endothelial dysfunction. Crosstalk between these pathways is under investigation.

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CHOLESTEROL LOWERING POTENTIALS OF A BLEND OF STANDARDIZED METHANOL EXTRACTS OF MORINGA OLEIFERA LEAVES AND FRUITS IN ALBINO WISTAR RATS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i11.14014 ◽

2016 ◽

Vol 8 (11) ◽

pp. 262

Author(s):

Gururaja G. M. ◽

Deepak Mundkinajeddu ◽

Senthil Kumar A. ◽

Joshua Allan J. ◽

Shekhar M. Dethe ◽

...

Keyword(s):

Moringa Oleifera ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

Inhibition Assay ◽

High Cholesterol ◽

Cholesterol Lowering ◽

Methanol Extracts ◽

Ionic Detergent ◽

Lipase Inhibition

Objective: Moringa oleifera Lam. (Moringaceae), a small rapid growing, evergreen, deciduous tree is an important medicinal plant. Leaves and fruits of this plant are used for various ailments, as a nutritional supplement and also as vegetables. The current study involves in the determination of best combination of the cholesterol-lowering potential of a blend of methanol extracts of M. oleifera leaf and fruits, developed based on in vitro FIC index studies and evaluate the combination of this extracts in hypercholesterolemic animal models.Methods: Leaf and fruit methanol extracts and their combinations were tested in in vitro lipase inhibition assay to determine the best combination using fractional inhibitory concentration (FIC) index. Hypercholesterolemia was induced with Triton WR-1339 (a non-ionic detergent) and with high cholesterol diet for acute and chronic model respectively and the cholesterol-lowering effect of 1:1 blend of M. oleifera leaf and fruits methanol extracts was evaluated.Results: The FIC index values indicated that M. oleifera leaf and fruit extracts blended in 1:1 proportion was the best combination in in vitro lipase inhibition assay. This blend, when evaluated in vivo, showed a significant decrease in serum total cholesterol level from 24 h through 48 h in triton model. In high cholesterol diet model, the extract blend showed a significant reduction in serum triglycerides levels at 3 and 6 w of treatment.Conclusion: The results indicate that the blend of M. oleifera at the tested dose could be lowering cholesterol and triglyceride levels by inhibiting the absorption of cholesterol and can be developed as a standardized blend for dietary supplement market.

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In vitro and in vivo cholesterol lowering ability of Lactobacillus pentosus KF923750

Beneficial Microbes ◽

10.3920/bm2016.0121 ◽

2017 ◽

Vol 8 (2) ◽

pp. 271-280 ◽

Cited By ~ 15

Author(s):

F. Bendali ◽

K. Kerdouche ◽

S. Hamma-Faradji ◽

D. Drider

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

High Cholesterol ◽

Lactobacillus Pentosus ◽

Survival Percentage

Lactobacillus pentosus KF923750 was characterised for probiotic related properties and then characterised for cholesterol uptake in vitro as well as in vivo using rabbits fed a high-cholesterol diet. The survival percentage of L. pentosus KF923750 was 100% at pH 3, 52.18% at pH 2 and 36.21% at pH 2 plus pepsin. Similarly, this strain appeared resistant to bile (0.1% [98.42%], 0.3% [88.52%], 0.5% [75.60%] and 1% [71.15%]), after 4 h exposure. Moreover, L. pentosus KF923750 controlled growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 through the production of a bacteriocin-like inhibitory substance and anti-adhesive capabilities. L. pentosus KF923750 was non-cytotoxic to eukaryotic cells but sensitive to some antibiotics. Compared with rabbits fed a high-cholesterol diet but without L. pentosus KF923750 supplementation, the plasma total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in L. pentosus KF923750-fed rabbits by 11.54, 16.00 and 18.00%, respectively, with no significant change in high-density lipoprotein cholesterol levels. The histological sections of livers revealed lesions in all the rabbits that were fed a high-cholesterol diet, but these were less pronounced in rabbits ingesting L. pentosus KF923750. This study highlights the potential of lactobacilli, such as L. pentosus KF923750, in the treatment or prevention of hypercholesterolemia.

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Hepatic lipase function and the accumulation of β-very-low-density lipoproteins in the plasma of cholesterol-fed rabbits

Biochemical Journal ◽

10.1042/bj2930745 ◽

1993 ◽

Vol 293 (3) ◽

pp. 745-750 ◽

Cited By ~ 13

Author(s):

S Chang ◽

J Borensztajn

Keyword(s):

Lipoprotein Lipase ◽

Hepatic Lipase ◽

Low Density Lipoproteins ◽

High Cholesterol Diet ◽

Low Density ◽

Cholesterol Diet ◽

High Cholesterol ◽

High Fat ◽

Very Low Density Lipoproteins

The accumulation of cholesterol-rich beta-very-low-density lipoproteins (beta-VLDL) in the plasma of rabbits fed on a high-fat high-cholesterol diet is due to a defect in the clearance of these lipoprotein remnants from circulation by the liver. In view of the evidence that hepatic lipase participates in the process of rapid removal of remnants from circulation, and considering that rabbits are naturally deficient in hepatic lipase, we examined whether this defect in the clearance of beta-VLDL could be reversed by exogenous hepatic lipase. We report that treatment in vitro of [3H]cholesterol-labelled beta-VLDL, or rat chylomicrons, with hepatic lipase resulted in the formation of particles that were rapidly cleared from circulation by the liver when injected intravenously into hypercholesterolaemic rabbits. These results are consistent with the notion that, in addition to the well-established requirement for lipoprotein lipase activity, the generation of remnants capable of being efficiently taken up by the liver also requires the action of hepatic lipase. Lipoprotein lipase acts on triacylglycerol-rich lipoproteins to transform them into particles (remnants) which bind to the surface of liver cells, where they become accessible to hepatic lipase. Hepatocyte endocytosis of these remnants occurs only after further modification by hepatic lipase. According to this scheme, the results presented suggest that the accumulation of beta-VLDL in the circulation of rabbits fed on a high-fat high-cholesterol diet is the result of the saturation of the available hepatic lipase by abnormally high levels of lipoprotein-lipase-generated chylomicron remnants.

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Improvement on high-cholesterol diet induced atherosclerosis, lipid profile, oxidative stress and genotoxicity in the liver of mice by Echinops spinosissimus Turra subsp. spinosus

10.21203/rs.3.rs-18432/v1 ◽

2020 ◽

Author(s):

Donyez Frikha Dammak ◽

Hajer Ben Saad ◽

Emna Bouattour ◽

Ons Boudawara ◽

Raoudha Mezghani Jarraya

Keyword(s):

Oxidative Stress ◽

Antioxidant Activities ◽

Dietary Cholesterol ◽

Atherogenic Index ◽

High Cholesterol Diet ◽

Antioxidant Compounds ◽

Cholesterol Diet ◽

High Cholesterol ◽

Oxidative Stress Biomarkers

Abstract Background Hypercholesterolemia is a major risk factor for the development of atherosclerosis and endothelial dysfunction. Methods The present study investigates the possible mechanism of Echinops spinosissimus Turra subsp. spinosus ( E. s. spinosus ) flower on the high cholesterol diet. Results Our in vitro results demonstrated the richness of E.s. spinosus flower in antioxidant compounds, and its antioxidant activities. The co-administration of E.s. spinosus (100 or 200 mg/kg/day) with high-fat diet attenuated hepatotoxicity as monitored by the improvement of oxidative stress biomarkers and plasma lipid and liver parameters, when compared to the hypercholesterolemic mice. Atherogenic index and body weight were also reduced markedly, compared to control mice. These results were confirmed by the improvement of histological changes and DNA damage. Conclusion These data indicate that E.s. spinosus flower reduces the hypercholesterolemia risk and atherogenic properties of dietary cholesterol. Its hypocholesterolemic effect may be due to its antioxidant activities and its richness in bioactive molecule.

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Oxidized Low-Density Lipoprotein-Deteriorated Psoriasis Is Associated with the Upregulation of Lox-1 Receptor and Il-23 Expression In Vivo and In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms19092610 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2610 ◽

Cited By ~ 5

Author(s):

Chun-Ming Shih ◽

Chien-Yu Huang ◽

Kuo-Hsien Wang ◽

Chun-Yao Huang ◽

Po-Li Wei ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

High Cholesterol Diet ◽

Low Density ◽

Hacat Cells ◽

Cholesterol Diet ◽

Oxidized Low Density Lipoprotein ◽

High Cholesterol ◽

Tnf Α

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoetm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-α-stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoetm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-α-stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.

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Evaluation of in vitro Cholesterol esterase inhibitory and in vivo Anti-hyperlipidemic activity of aqueous extract of Plukenetia conophora Mull. Arg. (Euphorbiaceae)

International Journal of Phytomedicine ◽

10.5138/09750185.2324 ◽

2019 ◽

Vol 11 (1) ◽

Author(s):

Glory Oluremilekun Ajayi ◽

Aleshe Modupe Nofisat ◽

Bassey Mfon Jessica

Keyword(s):

Aqueous Extract ◽

Cholesterol Esterase ◽

High Cholesterol Diet ◽

Phytochemical Analysis ◽

Cholesterol Diet ◽

High Cholesterol ◽

Edible Plant ◽

Standard Drug

Hyperlipidemia is a condition of abnormally high lipids levels in the blood which has been ranked as one of the greatest risk factors contributing to prevalence and severity of coronary heart disease. The available antihyperlipidemic drugs have been associated with some side effects however, herbal management of hyperlipidemia are relatively safe, cheap and readily available. P. conophora is an edible plant consumed in Nigeria as snack and speculated to have beneficial effect on blood lipid profile. The present study evaluates anti-hyperlipidemic effect of aqueous extract of cooked P. conophora nut using in vivo and in vitro experimental models.The anti-hyperlipidemic activity was evaluated using tyloxapol induced-hyperlipidemic rats by intraperitoneal injections of Tyloxapol at a dose of 300 mg/kg body weight and high cholesterol-diet induced rats by oral administration of high cholesterol diet for 60 days. Cholesterol esterase enzyme inhibition was used for the in vitro evaluation.Aqueous extract of P. conophora at varying doses, reduced the elevated lipid parameters in both models; the dose of 500 mg/kg showed comparable hypolipidemic effects with standard drug (Simvastatin) at 10 mg/kg (P<0.01). The extract also inhibited cholesterol esterase enzyme with IC50 value of 129.30±0.10μg/ml while Simvastatin with IC50 value of 51.42±0.13μg/ml. Preliminary phytochemical analysis revealed the presence of; Flavonoids, saponin, cardiac glycoside, alkaloids, tannins, steroids and reducing sugar.P. conophora extract exhibited strong hypolipidemic activity and the dose of 500mg/kg demonstrated equipotent activity as the standard drug; Simvastatin 10mg/kg. The extract also showed inhibitory activity against pancreatic cholesterol esterase enzyme; hence can be used to limit absorption of dietary cholesterol, prevent and treat hyperlipidemia.

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