Hypercholesterolemic Diet Research Articles

Fenugreek proteins and their hydrolysates prevent hypercholesterolemia and enhance the HDL antioxidant properties in rats

PurposeThis paper aims to investigate the in vivo hypocholesterolemic property of fenugreek proteins (FP), Purafect-fenugreek protein hydrolysate (PFPH) and Esperase-fenugreek protein hydrolysate (EFPH) on high cholesterol (HC)-fed rats.Design/methodology/approachRats were randomized into five groups: four were fed for four weeks a hypercholesterolemic diet and the tested products were given by gavage. The fifth group was taken as control (C) receiving the same diet without cholesterol.FindingsResults showed that the elevated aspartate aminotransferase activity in HC group plasma was significantly corrected by FP and EFPH administration (−33 per cent; p = 0.0003). HC liver lipids and total cholesterol (TC) contents were not markedly affected by FP and EFPH. However, liver triglycerides (TG) contents trended to decrease in FP rats vs HC (p = 0.07), while, the TG decrease was significant in groups fed the proteins hydrolysates (p = 0.02). On the other hand, serum TC and TG decreased by 53 per cent (p = 0.0003) and 20 per cent (p = 0.04), respectively, in FP treated rats compared to HC group. This decrease was associated with a high fecal cholesterol excretion (2.5-fold higher in FP vs HC; p = 0.0001). Likewise, EFPH-treated rats exhibited lower TC compared to HC rats (p = 0.004). The very low density lipoprotins was the main affected fraction in these two groups, while there were no significant difference in apolipoproteins (Apo) B, A-I and A-IV contents between the different groups, except in FP group, where Apo A-I and A-IV decreased by 26 and 17 per cent, respectively, compared to C rats (p = 0.02). The high density lipoproteins (HDL) of rats treated with proteins hydrolysates showed a better antioxidant property compared to those of HC rats, which was accompanied with an increase in paraoxonase activity when compared to HC group.Originality/valueUnlike PFPH which had almost no effect, FPs and EFPH could constitute a nutraceutical ingredient in cardiovascular disease management.

Anti-hypercholesterolemic effect of unripe Musa paradisiaca products on hypercholesterolemia-induced rats

Protective Effects of Vitamin-P and Vitamin-C on Hypercholesterolemia-induced Oxidative Hepatic Damage and Lipid Profile Changes in Female Rats: A Comparative StudyOsama A Alkhamees

The Effect of Melinjo Peel Extract in Activity of Lipoprotein Lipase Enzym of The Rats Fed a Hypercholesterolemia Diet

The intake of saturated fat and cholesterol that comes from food digested in the intestine resulting in free fatty acids, triglycerides, phospholipids, and cholesterol. Triglyceride levels increased can be caused by presence of impaired lipoprotein lipase (LPL) enzyme activity. LPL activity can be increased by flavonoid in plant, like Melinjo peel. The purpose of this study is to measure LPL enzyme activity before and after being given extract of Melinjo peel treatment. This research use true experimental, with study design of pretest posttest control group design. Hypercholesterolemic diet given to rats by oral gavage as much as 1,8 grams for 14 days. Melinjo peel extract were given by oral gavage for 14 days after the hypercholesterolemic diet is given. Statistical analysis used Paired Sample T-Test to compare lipoprotein lipase activity before and after treatment. Then, used MANOVA (Multivariate Analyses of Variance) to see the difference of lipoprotein lipase activity in each group after treatment.Based on statistical analysis showed that there were differences of lipoprotein lipase activity in the hypercholesterolemic diet group, HD+54.15, HD+108.30, and HD+216.60 before and after treatment significant (p. < 0.05). The activity of lipoprotein lipase in the normal diet group compared with the hypercholesterolemic and HD+216.60 group showed a significant difference (p. < 0.05). Melinjo peel extract can increased activity of lipoprotein lipase enzym after treatment, those can be due to the flavonoid in Melinjo peel extract.

Can a hypercholesterolemic diet change the basal brain electrical activity and during status epilepticus in rats?

The brain is an organ rich in lipids, including cholesterol, in which these lipids are associated to structure and brain function. Thus alterations in lipid levels of diets may interfere in the brain electrical activity. Our aim was to evaluate the interference of hypercholesterolemic diets in the brain electrical activity in normal individuals and with epilepsy. Histological analysis and electrocorticograms (ECoG) were performed in animals fed with and without hypercholesterolemic diet before and during the status epilepticus induced by pilocarpine. The power spectrum of ECoG was used to estimate the contribution of different brain rhythms in ECoG signal. The animals submitted to the status epilepticus showed cell death, vacuolization with destructuration of the cell layers. Both animal groups, those with status epilepticus and status epilepticus with hypercholesterolemic diet, showed cellular lesions similar. The hyperlipid diet promoted increase of brain electrical activity, this was revealed by increase in the average power of beta wave (14-30Hz) and decrease in the average power of the delta wave (0,5-4Hz). This increase of brain electrical activity was even higher when the animals were fed a hypercholesterolemic diet and submitted to status epilepticus. Animals fed with hypercholesterolemic diet and submitted to status epilepticus presented a higher increase in brain excitability compared to control animals. We observed that hypercholesterolemic diet favored a greater severity of the status epilepticus.

Green tea extract attenuates non alcoholic fatty liver disease by decreasing hyperlipidemia and enhancing Superoxide dismutase activity in cholesterol-fed rats

BACKGROUND/AIM: Health benefits of green tea for a wide variety of ailments, including the cancer, heart disease, and liver disease, were reported. It is believed to have beneficial effects in the prevention and treatment of many diseases, one of which is non-alcoholic fatty liver disease (NAFLD). This study inspects the protective effect of green tea against atherosclerosis and NAFLD in comparative approach between curative and preventive models. MATERIALS AND METHODS: Twenty four of Wistar rats were studied for 150 days. After 15 days of adaptation period, rats were divided into four groups including normal Group (NG), control Hypercholesterolemic diet Group (CHDG), preventive Group (PG) and curative Group (CG) that followed respectively the following regimens: 1 mL/kg of sunflower oil for 150 days, 1 mL/kg of cholesterol solution prepared at 1.5% (w/v) in sunflower oil span 150 days, 1 ml/kg of cholesterol solution at 1.5% (w/v) in sunflower oil with 3 mL/kg GTLE for 60 days and 1 mL/kg of cholesterol solution at 1.5% (w/v) in sunflower oil for 30 days followed by 3 mL/kg of GTLE for 30 days. These both PG and CG groups were ingested with cholesterol 1.5% (w/v) during remaining period. RESULTS: The results showed significant increase, except for NG, during the 30 first days (p≤0.001) in lipid serum profiles including Total Cholesterol (TC), Triacylglycerol (TG) and Low-Density Lipoprotein cholesterol (LDL-c). However, the High-Density Lipoprotein cholesterol (HDL-c) profile decreased during the treatment (p≤0.001). The ingestion of GTLE in treated groups (CG and PG) declined significantly (p≤0.001) in blood lipid concentrations (TC: 67%, TG: 23%, LDL-c: 81.12%) except for the HDL-c that increased up to 15%. The Atherogenic Index (AI) also decreased significantly (p≤0.001) up to 48%, in CG and PG. PG and NG marked same SOD activity values (130.91±7.66 versus 141.31±8.21 U/mL), while CG showed the lowest level. Liver sections were well protected in protective model than curative one.

Fast Morphological Gallbladder Changes Triggered by a Hypercholesterolemic Diet

Introduction and aim. Obesity is a worldwide epidemic problem, described as a risk factor for hepatic diseases, such as non-alcoholic fatty liver disease and other pathologies related to development of cholesterol crystals and cholesterol gallbladder stones. It has been reported that cholesterol overload may cause hepatic damage; however, little is known about the effects of an acute hypercholesterolemic diet on the gallbladder. The aim of this manuscript was to evaluate the impact of a cholesterol-rich diet on the gallbladder.Material and methods. The study included ten eight-week-old C57BL6 male mice, which were divided into two study groups and fed different diets for 48 h: a hypercholesterolemic diet and a balanced Chow diet. After 48 h, the mice were analyzed by US with a Siemens Acuson Antares equipment. Mice were subsequently sacrificed to carry out a cholesterol analysis with a Refloton System (Roche), a crystal analysis with a Carl Zeiss microscope with polarized light, and a histological analysis with Hematoxylin-eosin staining.Results. The hypercholesterolemic diet induced an increase in gallbladder size and total cholesterol content in the bile, along with important histological changes.Conclusion. Cholesterol overloads not only trigger hepatic damage, but also affect the gallbladder significantly.

Anti-hypercholesterolemic impacts of barley and date palm fruits on the ovary of Wistar albino rats and their offspring

A high cholesterol diet is related to ovarian dysfunction and infertility which has been increased among young ages consuming processed food products. The present study was conducted to evaluate the role of a high cholesterol diet on the ovaries of young female rats via assessments of histopathology, immunohistochemistry, oxidative stress and apoptic markers. Also, mating of hypercholesterolemic female rats was carried out to measure the fertility and numbers of their offspring. At the same time, phytotherapy was carried out through supplementing the diet with barley and/ or date palm fruits (10%) during the experiment to assess the phyto-therapeutic impacts in attenuation of drastic hypercholesterolemic effects.Hypercholesterolemic diet-fed rats exhibited damage of the ovarian follicles and increased follicular atresia. Furthermore, expression of cleaved caspase-3 was upregulated, while PCNA was downregulated in granulosa, theca and stroma cells. Hypercholesterolemic female rats showed marked depletion of antioxidative enzymes, increased lipid peroxidation and apoptotic markers. Alterations to the female serum hormones were detected. Offspring maternally fed on hypercholesterolemic diet showed a significant decrease of body weight and altered sex ratio. However, concomitant supplementation of barley and or date fruits to hypercholesterolemic groups revealed marked improvement of ovarian structure and function.On the basis of these evidences, it is believed that the enhanced synergistic effects of barley and/or date palm fruits in the amelioration of ovarian structure and functions were elicited by the potential antioxidant activity of their phytomicronutrients, polyphenols, β-glucan and trace elements. These materials scavenge free radicals from inflamed cells that can be used to establish an effective and novel therapeutic strategy for activating ovarian cell regeneration.

Administration of valine, leucine, and isoleucine improved plasma cholesterol and mitigated the preatherosclerotic lesions in rats fed with hypercholesterolemic diet

Abstract Hypercholesterolemia has a major contribution to the occurrence and progression of atherosclerotic lesions. Recent studies report the involvement of branched-chain amino acids in cholesterol methabolism. The aim of this research was to evaluate the role of valine, leucine and isoleucine on the occurrence and progression of atherosclerosis in rats receiving hypercholesterolic diet. Material and methods: 50 male Wistar rats distributed into five groups with the following type of diets: group I (control) received standard diet; group II - cholesterol; group III - cholesterol and valine; group IV - cholesterol and leucine; group V - cholesterol and isoleucine. The experimental study was conducted over a period of 2 months. The animals were evaluated for the serum levels of total cholesterol at the beginning of the experiment, after 1 month and after 2 months. The collected tissue fragments of heart and aorta were prepared for the examination by optical microscopy in order to identify the atherosclerotic changes. Results: The most increased values of serum cholesterol were recorded in rats from group II (p=0.001), for the second and third evaluation. The histological examination showed early histopathological lesions on the vascular intima for the groups treated with cholesterol, valine, leucine, and isoleucine. These early changes (the occurrence of some superficial endothelial erosions, adhesion of erythrocytes and platelets) were correlated with the degree of the arterial wall damage, of the leukocytes adhesion to the arterial intima, and the discontinuities of the internal elastic lamina. Conclusion: The comparative study of the effects of the three essential amino acids revealed that valine induced a faster response than leucine and isoleucine on the improvement of biochemical parameters, but there were no significant differences between the three amino acids in terms of their protective ability, demonstrated by the histopathological lesion assessment.

Modulation of Rat Liver Regeneration after Partial Hepatectomy by Dietary Cholesterol.

The aim of study was to evaluate impact of long-term dietary cholesterol overload on the cholesterol homeostasis and liver regeneration. Serum lipid parameters, 14C-cholesterol incorporation, liver DNA synthesis and protein expression was determined in partially hepatectomized (PH) rats fed with a standard (SLD) or hypercholesterolemic (CHOL) diet. 29-day intake of CHOL diet before PH produced increase in serum total cholesterol, LDL lipoprotein, and triglyceride concentration. PH provoked decrease in serum total cholesterol and triglyceride concentration in both groups. PH was associated with increase in serum ALT activity more pronounced in CHOL animals. Hepatic DNA synthesis was increased after PH in both groups, but lower in CHOL. Hypercholesterolemic diet reduced the absorption of radiolabelled cholesterol in intestine and then activity in blood and liver. The 14C-cholesterol hepatic activities tend to increase after PH in both groups. CHOL diet produced up-regulation of Acyl-CoA:cholesterol acyltransferase-2 protein expression. PH was associated with increase of LDL receptor and Acyl-CoA:cholesterol acyltransferase-2 protein expression in both dietary groups. Liver regeneration after PH is negatively influenced by CHOL diet. The increased uptake of cholesterol in the liver after PH associated with up-regulation of LDL receptor protein expression suggests preferential use of extrahepatic cholesterol by the liver.

Ultrasound Microbubble Delivery Targeting Intraplaque Neovascularization Inhibits Atherosclerotic Plaque in an APOE-deficient Mouse Model.

Intraplaque neovascularization is often associated with plaque formation, development and instability, and clinical symptoms in atherosclerosis. The aim of the present study was to investigate a new strategy for treating athrosclerosis by ultrasound-targeted microbubble delivery (UTMD) targeting intraplaque neovascularization in an APOE-deficient mouse model of atherosclerosis. A mouse model of atherosclerosis was induced by feeding Apoe-/- mice a hypercholesterolemic diet and was verified with hematoxylin and eosin staining and intercellular adhesion molecule 1 (ICAM-1) expression. Targeted microbubbles (MB) were prepared by conjugating microbubbles with biotinylated antibody to ICAM1 (MBi) or with both biotinylated anti-ICAM1 and the angiogenesis inhibitor Endostar (MBie). The targeted microbubbles were analyzed with epifluorescence microscopy and flow cytometry. The animals with induced atherosclerotic plaques received MBi or MBie followed by UTMD treatment. Endostar treatment alone was given to other animals for comparison. Morphological assessment of atherosclerotic plaques was performed after treatment. The expression of angiogenesis marker CD31 was detected by immunohistochemical analysis. Atherosclerotic plaques developed in the entire aorta with significant intraplaque ICAM-1 expression in the APOE-deficient mice following a 30-week hypercholesterolemic diet. Microbubbles were successfully conjugated with anti-ICAM-1 and Endostar, with a conjugation rate of 98.3% and 63.5%, respectively. UTMD with MBie significantly reduced the area of atherosclerotic plaque as compared to the model control (p<0.05). Treatment with Endostar and UTMD with MBie significantly reduced CD31 expression compared with the model control group (p<0.01). Greater significant inhibitory effect on CD31 expression was found in the group treated with UTMD and MBie compared to the Endostar- and UTMD with MBi groups (p<0.01). UTMD targeting intraplaque neovascularization was found to inhibit atherosclerotic plaque in a mouse model of atherosclerosis, suggesting the potential of microbubble-mediated ultrasound technology in aiding drug delivery for atherosclerosis treatment.

Effects of hydroalcoholic extract of Celtis iguanaea on markers of cardiovascular diseases and glucose metabolism in cholesterol-fed rats

Celtis iguanaea (Jacq.) Sarg., Cannabaceae, is popularly used in the treatment of diabetes mellitus. However, chemical and pharmacological investigations are lacking. In this study, we investigated the effects of the hydroalcoholic extract from C. iguanaea on markers of cardiovascular diseases and the glucose metabolism in cholesterol-fed rats. Therefore, hypercholesterolemic rats (1% cholesterol) were orally treated with C. iguanaea extract (C-150, CI-300, or CI-600mg/kg) or simvastatin (4mg/kg) (n=6) once a day (30 days) with a hypercholesterolemic diet. A control group (C) was given saline. C. iguanaea extract showed significant decreases in serum levels of total cholesterol, LDL-cholesterol, HMG-CoA-reductase, interleukin-1 and 6, TNF-α and IFN-γ when compared to group C (p<0.001). Hypoglycemic effects were observed along with a decrease of the activity of sucrase (CI-600), maltase (CI-150, CI-300), and an increase in muscle glycogen levels (CI-300). Antioxidant effects were observed in plasma by the decrease of TBARS and increase of nonprotein thiols levels (CI-600). The histopathological analysis showed a significant decrease in the liver fat area for C. iguanaea extract compared to group C (p<0.001). Our results suggest that the biological effects of C. iguanaea extract could be related to the flavonoids that possibly exert antioxidant, enzymatic inhibitory, and insulin-mimetic effects.

Lychee (Litchi chinensis Sonn.) peel flour: effects on hepatoprotection and dyslipidemia induced by a hypercholesterolemic diet

Dyslipidemias are associated with the incidence of cardiovascular diseases, obesity, diabetes, hypertension and hepatic steatosis, being the cause of morbidity and mortality. This study investigated the effects of lychee peel flour (PF) on serum levels of total cholesterol (TC), low-density lipoprotein (LDL-c), triacylglycerols (TAG) and various parameters related to obesity, in rats fed a hypercholesterolemic diet. Therefore, 20 male rats were used. In the first 21 days, the animals were fed a hypercholesterolemic diet, except for control group. In the following 21 days, their diets were modified, and they received a standard diet (Control); hypercholesterolemic (Hyper); hypercholesterolemic + 5% PF (PF5) and hypercholesterolemic + 10% PF (PF10). The results revealed that PF intake attenuated weight gain, reduced body mass index, glucose and the levels of TAG, TC, LDL-c, hepatic enzymes and leptin, besides the percentage of hepatic lipids, liver lipid peroxidation and frequency of severe steatosis. Histological studies of the aorta did not show the formation of the atheromatous plaque. These results reinforce its potential to reduce the risk of diseases associated with obesity.

The effects of oat bran and soy flour on humoral immune response in rats fed hypercholesterolaemic diets

Previous studies have demonstrated the immunological and hypercholesterolaemic effects of soluble dietary fibre and soy protein in rats. In this study, we evaluated the effects of oat bran and soy flour on humoral immune response in Wistar rats fed hypercholesterolaemic diets. Animals (6 groups) fed with different diets for 6 wks were inoculated twice with antigen (IgY). Plasma samples were collected after each inoculation and anti-IgY antibody (IgM, IgG1 and IgG2a) levels were evaluated by ELISA. Animals receiving 1% cholesterol presented an increase in anti-IgY IgG1 and a reduction in anti-IgY IgM and IgG2a relative to control animals. These effects were abrogated in animals fed 1% cholesterol and oat bran or oat bran+soy protein, but not in animals fed 1% cholesterol and soy protein. Diets containing 1% cholesterol resulted in hepatic lesions and higher liver and spleen relative weights, but did not affect lipid profile, weight gain, food intake, or food conversion efficiency. In conclusion, a high-cholesterol diet influences classes of antibodies produced in response to an antigen in a way that can be reversed by oat bran.

Can measurement of the fluorescence lifetime of extracted blood PPIX predict atherosclerosis?

In this work, fluorescence lifetime has been used to analyze protoporphyrin IX (PPIX) extracted from blood for diagnosing atherosclerosis. A total of 10 adult white male rabbits (New Zealand) were divided into the control group (CG), with a normal diet, and the experimental group (EG), subjected to a diet containing 1% cholesterol. Blood samples were collected from the animals, and protoporphyrin IX was extracted from the blood using acetone. The PPIX fluorescence lifetime (PPIXFL) was measured using time-correlated single photon counting, after excitation at 403nm from a pulsed laser diode. It was found that the PPIX emission intensity was enhanced in the animals that had received a hypercholesterolemic diet. The CG and EG animal's fluorescence decays were fitted by three exponentials and the mean lifetimes were 4.0ns and 9.5ns, respectively. This lifetime dependence resulted in a calibration curve that allows the determination of the PPIX concentration with a temporal measurement. The obtained results show that fluorescence lifetime can potentially be used as a noninvasive, simple, rapid, and sensitive tool in atherosclerosis diagnosis.

Polysaccharide‐rich hydrolysate from Saccharomyces cerevisiae (LipiGo®) increases fatty acid and neutral sterol excretion in guinea pigs fed with hypercholesterolemic diets

This study aimed to evaluate the hypolipidemic properties of a polysaccharide‐rich hydrolysate from Saccharomyces cerevisiae comprising β‐glucan‐chitin‐chitosan (BCC). Guinea pigs (n = 8 per group) were fed high‐fat and hypercholesterolemic diets (17 g/100 g of fat, 0.2 g/100 g of cholesterol), containing 12 g/100 g of either cellulose (CEL) as negative control, oat bran as a source of β‐glucan (BOB), or BCC. Food intake and body weight were monitored for 4 weeks and fatty acid (FA), neutral sterol (NS), and bile acid (BA) excretion were determined. BCC, but not BOB, reduced body weight gain and plasma total and LDL‐cholesterol, without altering food consumption. This effect correlated well with the capacity of BCC to reduce apparent FA absorption (78.36 ± 7.41 vs. 89.51 ± 3.93% in control group), mainly due to an increase of saturated fatty acid (SFA) excretion and, to a lower extent of monounsaturated fatty acids (MUFA). NS excretion was also increased by BCC, although no effects were observed on BA excretion. Therefore, results suggest that the hypolipidemic effect of BCC can be mainly ascribed to its capacity to increase FA and NS excretion.Practical applications: This research provides evidence on the hypolipidemic effect and mechanism of action of Lipigo®, a polysaccharide‐rich hydrolysate from Saccharomyces cerevisiae comprising β‐glucan‐chitin‐chitosan (BCC). Particularly, results show that BCC can effectively increase the excretion of saturated fatty acids (SFA) and neutral sterols (NS), having a beneficial effect on plasma lipids. This information can be of interest for the development of food supplements in the field of diseases associated with high fat intake such as cardiovascular diseases and obesity.Supplementation of hypercholesterolemic diets with a polysaccharide‐rich hydrolysate from Saccharomyces cerevisiae comprising β‐glucan‐chitin‐chitosan increases the excretion of saturated and monounsaturated fatty acids and neutral sterols compared to cellulose. This effect is consistent with a reduction in body weight gain and plasma total and LDL‐cholesterol.

Antihypercholesterolemic, antioxidant and renal protective effects of Mengkudu (Rubiaceae) fruit in nephropathy-induced albino rats.

To assess the modulatory impact of alcoholic extract of fruit of Mengkudu (AEFM, Morinda citrifolia L., Rubiaceae) on renal oxido-lipidemic stress in hypercholesterolemic albino rats. Twenty-four male albino rats were randomly divided into four groups with six rats in each group: group I as control, group II fed with hypercholesterolemic diet (HCD) for 45 days (4% cholesterol and 1% cholic acid), Group III rats fed with HCD for 45 days + AEFM (300 mg/kg body weight/day orally) for last 30 days and group IV normal rats fed AEFM alone. The blood was collected using ethylenediamine tetraacetic acid (EDTA) as an anticoagulant for various biochemical analysis, and excision of kidney was done for histological analysis. The levels of total cholesterol (TC), triacylglycerol (TG), phospholipids (PLs), renal functional parameters and lipid peroxidation products were markedly mitigated in AEFM treated hypercholesterolemic rats (group III) compared to group I (P<0.01). Activities of both enzymic and non-enzymic free radical scavenging factors were significantly increased in group III compared to group I (P<0.01). In group III the mRNA levels of interstitial endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) genes were obviously up-regulated (P<0.01) and down-regulated in (P<0.05) compared with group I. Histomorphological observations also exhibited similar as in group III AEFM commendably protects the renal tissues compared with group I (P<0.01). AEFM can act as nephroprotective agent by attenuating the renal oxidative stress, lipid levels as well as regulating NOS level and by this means protects the kidney in hypercholesterolemic induced nephropathy experimental rats.

Augmented Th17 differentiation in Trim21 deficiency promotes a stable phenotype of atherosclerotic plaques with high collagen content.

Patients with hyperlipidemia are at risk of atherosclerosis, but not all develop cardiovascular disease, highlighting the importance of other risk factors such as inflammation. Both the innate and adaptive arms of the immune system have been suggested in the initiation and propagation of plaque formation. Tri-partite motif (TRIM) 21 is a regulator of tissue inflammation and pro-inflammatory cytokine production, and has been implicated in chronic inflammatory disease. Here, we investigate a potential role for TRIM21 in coronary artery disease. Trim21-deficient or wild-type bone marrow was transplanted into Ldlr-/- mice fed a hypercholesterolemic diet. The Trim21-/-->Ldlr-/- mice developed larger atherosclerotic plaques, with significantly higher collagen content compared to mice transplanted with wild-type cells. High collagen content of the atheroma is stabilizing, and has recently been linked to IL-17. Interestingly, Trim21-/-->Ldlr-/- mice had elevated CD4 and IL-17 mRNA expression in plaques, and increased numbers of activated CD4+ T cells in the periphery. An increased differentiation of naïve T cells lacking Trim21 into Th17 cells was confirmed in vitro, with transcriptomic analysis revealing upregulation of genes of a non-pathogenic Th17 phenotype. Also, decreased expression of matrix metalloproteinases (MMPs) was noted in aortic plaques. Analysis of human carotid plaques confirmed that TRIM21 expression negatively correlates with the expression of key Th17 genes and collagen, but positively to MMPs also in patients, linking our findings to a clinical setting. In this study, we demonstrate that TRIM21 influences atherosclerosis via regulation of Th17 responses, with TRIM21 deficiency promoting IL-17 expression and a more fibrous, stable, phenotype of the plaques.

Endothelial dysfunction in experimental models of metabolic syndrome − effect of fructose

Abstract The aim of the work was to find an experimental model suitable for the study of endothelial dysfunction induced by MS. We used hypertriglyceridemic rats (HTG) that were fed a hypercholesterolemic diet of different composition and duration: a 6-week administration of standard diet with an addition of cholesterol and fat (HTGChol) and a three-month administration of the same diet with an addition of fructose (HTGCholF). We investigated the effect of different diets on aortic endothelial function. The standard diet fed Wistar (W) and HTG rats served as controls. Decision for addition of fructose to HTGChol was done based on in vitro experiments evaluating the effect of high concentration of saccharide in the incubation solution on aortic endothelial function. This intervention caused significant deterioration of relaxation induced by acetylcholine (ACh). While in HTGChol, we did not find significant differences in the function of the aorta compared to W or HTG rats, adding of fructose to high fat diet and prolonging its administration resulted in significantly impaired endothelium-dependent relaxation. It seems that such a model is suitable for the study of endothelial dysfunction in MS and the effect of substances that may protect the endothelium.

Zebra blenny protein hydrolysates as a source of bioactive peptides with prevention effect against oxidative dysfunctions and DNA damage in heart tissues of rats fed a cholesterol-rich diet

High-cholesterol diet (HCD) is suspected to produce in excess free radicals having adverse effects on human health and causing atherosclerosis damage in heart tissues. In our study, the effects of zebra blenny protein hydrolysates (ZBPHs) were investigated on cardiac oxidant/antioxidant status as well as DNA damage and histopathological disorders in rats, fed with a hypercholesterolemic diet. The molecular weight distribution of the hydrolysates was determined by size exclusion chromatography, which analyzed a representative hydrolysate type with a weight range of 3–20kDa. ZBPHs effectively protected heart genomic DNA against oxidative damage induced by Fenton's reagent. HCD promoted oxidative stress with a rise in serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities and thiobarbituric acid reactive substance (TBARS), advanced oxidation protein product (AOPP) and hydrogen peroxide (H2O2) levels in heart tissues. An increase in glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities as well as a fall in ATPase activities and glutathione (GSH) level was also noted in heart of hypercholesterolemic rats. Treatment with ZBPHs ameliorated the biochemical parameters cited above. In addition, pre-treatment with ZBPHs prevented DNA fragmentation. The histopathological findings confirmed the biochemical results and the potential antioxidant activities of ZBPHs which can help the cure and management of cardiovascular diseases induced by high-cholesterol levels.

Chemopreventive effects of a Tamarindus indica fruit extract against colon carcinogenesis depends on the dietary cholesterol levels in hamsters

Tamarind has significant antioxidant potential. We showed that tamarind protects hypercholesterolemic hamsters from atherosclerosis. Hypercholesterolemia might increase the risk of colon cancer. We investigated whether tamarind extract modulates the risk of colon cancer in hypercholesterolemic hamsters. Hamsters (n = 64) were given tamarind and a hypercholesterolemic diet for 8 weeks. The groups were the control, tamarind treatment, hypercholesterolemic, and hypercholesterolemic treated with tamarind groups. Half of each group was exposed to the carcinogen dimethylhydrazine (DMH) at the 8th week. All hamsters were euthanatized at the 10th week. In carcinogen-exposed hypercholesterolemic hamsters, tamarind did not alter the cholesterol or triglyceride serum levels, but it reduced biomarkers of liver damage (alanine transaminase [ALT], and aspartate aminotransferase [AST]). Tamarind decreased DNA damage in hepatocytes, as demonstrated by analysis with an anti-γH2A.X antibody. In liver and serum samples, we found that this fruit extract reduced lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) and increased endogenous antioxidant mechanisms (glutathione peroxidase [GPx] and superoxide dismutase [SOD]). However, tamarind did not alter either lipid peroxidation or antioxidant defenses in the colon, which contrasts with DMH exposure. Moreover, tamarind significantly increased the stool content of cholesterol. Although tamarind reduced the risk of colon cancer in hypercholesterolemic hamsters that were carcinogenically exposed to DMH by 63.8% (Metallothionein), it was still ∼51% higher than for animals fed a regular diet. Staining colon samples with an anti-γH2A.X antibody confirmed these findings. We suggest that tamarind has chemoprotective activity against the development of colon carcinogenesis, although a hypercholesterolemic diet might impair this protection.