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1.
Molecules ; 27(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35889272

RESUMO

The aim of the study was to evaluate the effect of the addition of Fagopyrum esculentum Moench buckwheat sprouts modified with the addition of Saccharomyces cerevisiae var. boulardii to an atherogenic diet on the metabolism of sterols and fatty acids in rats. It was noticed in the study that the group fed with modified sprouts (HFDPRS) had a greater amount of sterols by 75.2%, compared to the group fed on an atherogenic diet (HFD). The content of cholesterol in the liver and feces was lower in the HFDPRS group than the HFD group. In the serum of the HFDPRS group, a more significant amount of the following acids was observed: C18:2 (increase by 13.5%), C20:4 (increase by 15.1%), and C22:6 (increase by 13.1%), compared to the HFDCS group. Regarding the biochemical parameters, it was noted that the group fed the diet with the addition of probiotic-rich sprouts diet had lower non-HDL, LDL-C and CRP ratios compared to the group fed the high-fat diet. The obtained results indicate that adding modified buckwheat sprouts to the diet by adding the probiotic strain of the yeast may have a significant impact on the metabolism of the indicated components in the organism.


Assuntos
Fagopyrum , Fitosteróis , Saccharomyces boulardii , Animais , Dieta Aterogênica , Fagopyrum/química , Ácidos Graxos , Ratos , Saccharomyces cerevisiae , Esteróis
2.
Alcohol Clin Exp Res ; 46(7): 1192-1203, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35491473

RESUMO

BACKGROUND: Nonalcoholic steatohepatitis is the inflammatory subtype of nonalcoholic fatty liver disease with a high risk of progression to liver fibrosis. We investigated metabolic steatohepatitis with advanced liver fibrosis in apolipoprotein E/low-density lipoprotein receptor double-knockout (AL) mice fed a co-diet of ethanol with a low-carbohydrate-high-protein-high-fat atherogenic diet (AD) for 16 weeks. We also examined the underlying mechanisms, especially hepatic sympathetic activation, involved in the effects. METHODS: We maintained 12-week-old male AL mice on AD and a standard chow diet (SCD) with or without ethanol treatment for 16 weeks. Age-matched male C57BL/6J mice on SCD without ethanol treatment served as controls. We conducted blood biochemical, histopathological, and fluorescence immunohistochemical, and reverse transcriptase polymerase chain reaction studies. RESULTS: AL mice showed significant hyperlipidemia. AD induced increased body weight, hepatic steatosis, and hepatic damage; ethanol and the AD co-diet resulted in hepatic sympathetic activation accompanied by hepatic steatosis, lobular inflammation, bridging fibrosis, and hepatic damage. Hepatic Kupffer cells (KCs) and hepatic stellate cells (HSCs), which showed sympathetic activation, produced 4.4- to 9.4-fold more inflammatory factors (KC and KC-derived tumor necrosis factor-α, and chemokine [C-C motif] ligand 2) and 2.0- to 32.0-fold more fibrosis factors (HSC and HSC-derived transforming growth factor ß1 and collagen 1a1); all p < 0.05 vs. controls. CONCLUSIONS: We created a model of metabolic steatohepatitis with advanced liver fibrosis from coexisting hyperlipidemia and hepatic sympathetic activation in AL mice on a co-diet of ethanol and AD. KCs and HSCs became the cellular targets of hepatic sympathetic activation, which could play a role in the initiation and progression of metabolic steatohepatitis with advanced liver fibrosis.


Assuntos
Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Aterogênica , Modelos Animais de Doenças , Etanol/toxicidade , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , Fígado/metabolismo , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/metabolismo
3.
Nutrients ; 14(6)2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35334930

RESUMO

Cardiovascular disease has one of the highest global incidences and mortality rates. Atherosclerosis is the main cause of cardiovascular disease, and hypercholesterolaemia and hyperlipidaemia are the main risk factors for the development of atherosclerosis. Decreasing serum cholesterol and triglyceride concentrations is considered to be an effective strategy to prevent atherosclerotic cardiovascular disease. Previous studies have shown that many diseases are related to gut microbiota dysbiosis. The positive regulation of the gut microbiota by probiotics may prevent or treat certain diseases. In this study, Lactobacillus reuteri CCFM8631 treatment was shown to decrease plasma total cholesterol (TC), low-density lipoprotein-cholesterol, aspartate transaminase, alanine transaminase and trimethylamine N-oxide concentrations, decrease liver TC and malondialdehyde concentrations and recover liver superoxide dismutase concentrations in mice fed a Paigen atherogenic diet. In addition, L. reuteri increased the faecal short-chain fatty acid content (acetate, propionate and butyrate), which was accompanied by an increase in the relative abundance of faecal Deferribacteres, Lachnospiraceae NK4A136 group, Lactobacillus and Dubosiella; a decrease in the relative abundance of Erysipelatoclostridium and Romboutsia and the activation of butanoate and vitamin B6 metabolism, leading to the alleviation of hypercholesterolaemia.


Assuntos
Microbioma Gastrointestinal , Hipercolesterolemia , Hiperlipidemias , Lactobacillus reuteri , Animais , Dieta Aterogênica , Hiperlipidemias/etiologia , Lactobacillus reuteri/fisiologia , Camundongos
4.
Acta sci., Health sci ; 44: e58558, Jan. 14, 2022.
Artigo em Inglês | LILACS | ID: biblio-1367771

RESUMO

Cardiovascular disease(CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects.This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard foodand receiving by gavage virgin olive oil (HCD+VOO) and(4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low­Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High­Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.


Assuntos
Animais , Ratos , Estresse Oxidativo/imunologia , Aterosclerose/dietoterapia , Dieta Hiperlipídica/métodos , Azeite de Oliva/farmacologia , Triglicerídeos/farmacologia , Peroxidação de Lipídeos/imunologia , Colesterol/farmacologia , Ratos Wistar/imunologia , Dieta Aterogênica/métodos , Glutationa/farmacologia , Hipercolesterolemia/imunologia , Lipoproteínas/imunologia
5.
Nutrients ; 13(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34836133

RESUMO

Bulbs from the Alliaceae family have been well-known and valued spices for thousands of years, not only for their unique flavor and aroma features, but also for their high nutritional and health-promoting values. Long-term or excessive consumption of these vegetables, especially raw garlic, can have side effects in the body (including in the digestive tract), causing a number of pathological changes in the intestinal wall; these changes lead, in turn, to its damage, dysfunction, and disorder development. Therefore, the aim of this study was to investigate the effect of the addition of freeze-dried vegetables from the Alliaceae family, i.e., garlic (Allium sativum L.), white onion, and red onion (Allium cepa L.) on the morphometric parameters (intestinal villi length, crypt depth, thickness of tunica mucosa, and the thickness of tunica muscle) of the jejunum of rats fed a semi-synthetic atherogenic diet (1% dietary cholesterol). In freeze-dried vegetables administered to rats, the contents of selected bioactive ingredients and their antioxidant potentials were determined. The effect of the onion vegetable supplements on growth parameters, serum lipid profile, plasma antioxidant potential, and the intestinal morphological parameters of rats loaded with cholesterol was determined. In an animal experiment, 30 male Wistar rats were divided into 5 diet groups, diet consumption and FER were studied. Supplementation of the atherogenic diet with vegetables improved the blood plasma lipid profiles and atherogenic indices, in a manner that was dependent on the type of supplementation used, with the best hypolipidemic and anti-atherosclerotic effects found in garlic use. The atherogenic diet, as well as the supplementation of this diet with the tested vegetables from the Alliaceae family, influenced the histological changes in the epithelium of the jejunum of rats. The damage to the intestinal mucosa was the greatest in animals fed an atherogenic diet supplemented with garlic. Bearing in mind that the desired beneficial therapeutic or prophylactic effects of onion vegetables (in particular garlic) in the course of various metabolic ailments (including atherosclerosis) are achieved during long-term supplementation, it is important to remember their possible cytotoxic effects (e.g., on the digestive tract) in order to achieve real benefits related to the supplementation with vegetables from the Alliaceae family.


Assuntos
Allium/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Alho/efeitos adversos , Mucosa Intestinal/patologia , Jejuno/patologia , Animais , Dieta Aterogênica/efeitos adversos , Masculino , Ratos , Ratos Wistar , Verduras/efeitos adversos
6.
Am J Physiol Endocrinol Metab ; 321(5): E689-E701, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34632798

RESUMO

Inflammation and dyslipidemia are often present in polycystic ovary syndrome (PCOS). We determined the effect of saturated fat ingestion on circulating heat shock protein-70 (HSP-70) and mononuclear cell (MNC) toll-like receptor-2 (TLR2) gene expression, activator protein-1 (AP-1) activation, and matrix matalloproteinase-2 (MMP-2) protein in women with PCOS. Twenty reproductive-age women with PCOS (10 lean, 10 with obesity) and 20 ovulatory controls (10 lean, 10 with obesity) participated in the study. HSP-70 was measured in serum and TLR2 mRNA and protein, AP-1 activation, and MMP-2 protein were quantified in MNC from blood drawn while fasting and 2, 3, and 5 h after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (ISOGTT). Androgen secretion was assessed from blood drawn while fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration. In response to saturated fat ingestion, serum HSP-70, TLR2 gene expression, activated AP-1, and MMP-2 protein were greater in lean women with PCOS compared with lean controls and in women with PCOS and obesity compared with controls with obesity. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects of their respective weight classes. Lipid-stimulated proatherogenic inflammation marker responses were negatively correlated with ISOGTT and positively correlated with abdominal adiposity and HCG-stimulated androgen secretion. In PCOS, saturated fat ingestion stimulates proatherogenic inflammation independent of obesity. This effect is greater when PCOS is combined with obesity compared with obesity alone. Abdominal adiposity and hyperandrogenism may perpetuate proatherogenic inflammation.NEW & NOTEWORTHY This paper demonstrates that in polycystic ovary syndrome (PCOS), ingestion of saturated fat triggers a molecular pathway of inflammation known to drive atherogenesis. This effect is independent of obesity as it occurs in lean women with PCOS and not in lean ovulatory control subjects. Furthermore, the combined effects of PCOS and obesity are greater compared with obesity alone.


Assuntos
Aterosclerose/etiologia , Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Inflamação/etiologia , Síndrome do Ovário Policístico/complicações , Adolescente , Adulto , Aterosclerose/patologia , Composição Corporal/efeitos dos fármacos , Dieta Aterogênica/efeitos adversos , Progressão da Doença , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Inflamação/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Síndrome do Ovário Policístico/patologia , Adulto Jovem
7.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806236

RESUMO

Classic atherosclerosis risk factors do not explain all cases of chronic heart disease. There is significant evidence that gut microbiota may influence the development of atherosclerosis. The widespread prevalence of chronic Helicobacter pylori (H. pylori, HP) infections suggests that HP can be the source of components that stimulate local and systemic inflammatory responses. Elevated production of reactive oxygen species during HP infection leads to cholesterol oxidation, which drives atherogenesis. The aim of this study is to explore the link between persistent HP infection and a high-fat diet in the development of proinflammatory conditions that are potentially proatherogenic. An in vivo model of Caviae porcellus infected with HP and exposed to an experimental diet was investigated for the occurrence of a proinflammatory and proatherogenic endothelial environment. Vascular endothelial primary cells exposed to HP components were tested in vitro for oxidative stress, cell activation and apoptosis. The infiltration of inflammatory cells into the vascular endothelium of animals infected with HP and exposed to a high-fat diet was observed in conjunction with an increased level of inflammatory markers systemically. The arteries of such animals were the least elastic, suggesting the role of HP in arterial stiffness. Soluble HP components induced transformation of macrophages to foam cells in vitro and influenced the endothelial life span, which was correlated with Collagen I upregulation. These preliminary results support the hypothesis that HP antigens act synergistically with a high-fat diet in the development of proatherogenic conditions.


Assuntos
Dieta Aterogênica , Dieta Hiperlipídica , Endotélio Vascular/metabolismo , Infecções por Helicobacter/complicações , Animais , Anticorpos Antibacterianos/imunologia , Aterosclerose/etiologia , Aterosclerose/microbiologia , Modelos Animais de Doenças , Células Endoteliais/microbiologia , Feminino , Células Espumosas/metabolismo , Células Espumosas/microbiologia , Gastrite/metabolismo , Gastrite/microbiologia , Cobaias , Helicobacter pylori , Células Endoteliais da Veia Umbilical Humana , Humanos , Imunoglobulina G , Inflamação , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Rigidez Vascular
8.
Physiol Genomics ; 53(5): 173-192, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33818129

RESUMO

Mice have provided critical mechanistic understandings of clinical traits underlying metabolic syndrome (MetSyn) and susceptibility to MetSyn in mice is known to vary among inbred strains. We investigated the diet- and strain-dependent effects on metabolic traits in the eight Collaborative Cross (CC) founder strains (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Liver transcriptomics analysis showed that both atherogenic diet and host genetics have profound effects on the liver transcriptome, which may be related to differences in metabolic traits observed between strains. We found strain differences in circulating trimethylamine N-oxide (TMAO) concentration and liver triglyceride content, both of which are traits associated with metabolic diseases. Using a network approach, we identified a module of transcripts associated with TMAO and liver triglyceride content, which was enriched in functional pathways. Interrogation of the module related to metabolic traits identified NADPH oxidase 4 (Nox4), a gene for a key enzyme in the production of reactive oxygen species, which showed a strong association with plasma TMAO and liver triglyceride. Interestingly, Nox4 was identified as the highest expressed in the C57BL/6J and NZO/HILtJ strains and the lowest expressed in the CAST/EiJ strain. Based on these results, we suggest that there may be genetic variation in the contribution of Nox4 to the regulation of plasma TMAO and liver triglyceride content. In summary, we show that liver transcriptomic analysis identified diet- or strain-specific pathways for metabolic traits in the Collaborative Cross (CC) founder strains.


Assuntos
Camundongos de Cruzamento Colaborativo/genética , Camundongos de Cruzamento Colaborativo/metabolismo , Dieta , Fígado/fisiologia , Animais , Dieta Aterogênica/efeitos adversos , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Patrimônio Genético , Fígado/metabolismo , Metilaminas/sangue , Camundongos Endogâmicos C57BL , NADPH Oxidase 4/genética , Triglicerídeos/metabolismo
11.
J Nutr ; 151(4): 902-910, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33561256

RESUMO

BACKGROUND: Epidemiologic studies suggest that fruit and vegetable (F&V) consumption is inversely associated with incidence of cardiovascular disease (CVD). However, evidence for causality is lacking, and the underlying mechanisms are not well understood. OBJECTIVES: We aimed to determine whether there is a causal relation between consuming high levels of F&V and prevention of atherosclerosis, the hallmark of CVD pathogenesis. Furthermore, the underlying mechanisms were determined. METHODS: Six-week-old male LDL receptor-knockout mice were randomly assigned to 3 diet groups (12 mice/group) for 20 wk: control (CON, 10% kcal fat, 0.20 g/kg cholesterol), atherogenic (Ath, 27% kcal fat, 0.55 g/kg cholesterol), and Ath supplemented with 15% F&V (Ath + FV) (equivalent to 8-9 servings/d in humans). F&V was added as a freeze-dried powder that was prepared from the 24 most commonly consumed F&Vs in the United States. Body weight, aortic atherosclerotic lesion area, hepatic steatosis area, serum lipid profile and proinflammatory cytokine TNF-α concentrations, gut microbiota, and liver TNF-α and fatty acid synthase (Fasn) mRNA concentrations were assessed. RESULTS: F&V supplementation did not affect weight gain. Mice fed the Ath + FV diet had a smaller aortic atherosclerotic lesion area (71.7% less) and hepatic steatosis area (80.7% less) than those fed the Ath diet (both P < 0.001) independent of impact on weight, whereas no difference was found between Ath + FV and CON groups in these 2 pathologic markers. Furthermore, F&V supplementation prevented Ath diet-induced dyslipidemia (high concentrations of serum TG and VLDL cholesterol and lower concentrations of HDL cholesterol), reduced serum TNF-α concentration (by 21.5%), suppressed mRNA expression of liver TNF-α and Fasn, and ameliorated Ath-induced gut microbiota dysbiosis. CONCLUSIONS: Our results indicate that consuming a large quantity and variety of F&Vs causally attenuates diet-induced atherosclerosis and hepatic steatosis in mice. These effects of F&Vs are associated with, and may be mediated through, improved atherogenic dyslipidemia, alleviated gut dysbiosis, and suppressed inflammation.


Assuntos
Aterosclerose/dietoterapia , Aterosclerose/prevenção & controle , Frutas , Receptores de LDL/deficiência , Verduras , Animais , Aterosclerose/etiologia , Dieta Aterogênica/efeitos adversos , Suplementos Nutricionais , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Fatores de Risco de Doenças Cardíacas , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Receptores de LDL/genética , Fator de Necrose Tumoral alfa/sangue , Aumento de Peso
12.
Toxicol Appl Pharmacol ; 415: 115430, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33524446

RESUMO

Air pollutants may increase risk for cardiopulmonary disease, particularly in susceptible populations with metabolic stressors such as diabetes and unhealthy diet. We investigated effects of inhaled ozone exposure and high-cholesterol diet (HCD) in healthy Wistar and Wistar-derived Goto-Kakizaki (GK) rats, a non-obese model of type 2 diabetes. Male rats (4-week old) were fed normal diet (ND) or HCD for 12 weeks and then exposed to filtered air or 1.0 ppm ozone (6 h/day) for 1 or 2 days. We examined pulmonary, vascular, hematology, and inflammatory responses after each exposure plus an 18-h recovery period. In both strains, ozone induced acute bronchiolar epithelial necrosis and inflammation on histopathology and pulmonary protein leakage and neutrophilia; the protein leakage was more rapid and persistent in GK compared to Wistar rats. Ozone also decreased lymphocytes after day 1 in both strains consuming ND (~50%), while HCD increased circulating leukocytes. Ozone increased plasma thrombin/antithrombin complexes and platelet disaggregation in Wistar rats on HCD and exacerbated diet effects on serum IFN-γ, IL-6, KC-GRO, IL-13, and TNF-α, which were higher with HCD (Wistar>GK). Ex vivo aortic contractility to phenylephrine was lower in GK versus Wistar rats at baseline(~30%); ozone enhanced this effect in Wistar rats on ND. GK rats on HCD had higher aortic e-NOS and tPA expression compared to Wistar rats. Ozone increased e-NOS in GK rats on ND (~3-fold) and Wistar rats on HCD (~2-fold). These findings demonstrate ways in which underlying diabetes and HCD may exacerbate pulmonary, systemic, and vascular effects of inhaled pollutants.


Assuntos
Poluentes Atmosféricos/toxicidade , Aorta Torácica/efeitos dos fármacos , Colesterol na Dieta/toxicidade , Diabetes Mellitus Tipo 2/complicações , Dieta Aterogênica/efeitos adversos , Lesão Pulmonar/induzido quimicamente , Pulmão/efeitos dos fármacos , Ozônio/toxicidade , Doenças Vasculares/induzido quimicamente , Animais , Aorta Torácica/metabolismo , Aorta Torácica/fisiopatologia , Biomarcadores/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Colesterol na Dieta/metabolismo , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Exposição por Inalação , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/sangue , Lesão Pulmonar/patologia , Masculino , Necrose , Edema Pulmonar/sangue , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/patologia , Ratos Wistar , Doenças Vasculares/sangue , Doenças Vasculares/fisiopatologia , Vasoconstrição/efeitos dos fármacos
13.
J Ethnopharmacol ; 269: 113701, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33346028

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Schinus terebinthifolius is traditionally used for its anti inflammatory capacity, and indicated as a cardioprotective agent, whereas, its preventive effect against atherogenic diet fed (AD) induced metabolic disorders and the underlying mechanisms has not yet been explored. AIM OF THE STUDY: This study was undertaken to investigate the ameliorative role of Schinus terebinthifolius fruits extract (STFE) against cardiovascular problem, oxidative and inflammatory status related to obesity in rats fed an atherogenic diet. MATERIALS AND METHODS: The metabolites profile in STFE was evaluated using HPLC-DAD-ESI-QTOF-MS/MS analysis. In Wistar rats, atherogenic diet was added for 9 weeks to induce lipid accumulation simultaneously with STFE (50 mg/kg b. w) or saline treatment. Biochemical, oxidant, and inflammatory criteria together with hepatic and arterial integrity examination were assessed. RESULTS: A total of thirty three metabolites were identified using HPLC-DAD-ESI-QTOF-MS, among them masazino-flavanone was the major compound (2645.50 µg/g DW). The results indicated that STFE supplementation during 9 weeks (50 mg/kg b. w.) significantly attenuated the altered lipid profile by decreasing the levels of TC, TG, LDL-C and increasing the HDL-C content both in plasma and liver, when compared with the AD-group. The histological analysis using ORO staining revealed a decrease in the lipid droplet deposit in the cytoplasm of hepatocytes of STFE + AD group. The addition of STFE could improve the glycemic status of AD-treated rats by decreasing the glucose and insulin secretion, and ameliorating the hepatic glycogen synthesis. The harmful effects of atherogenic diet on hepatic oxidative stress indicators (MDA, PC, GSH, SOD, CAT, and GPx), biochemical markers (AST, ALT, LDH and ALP), and liver function, were found to be decreased by the addition of STFE. Moreover, the reduction of inflammatory markers (CRP, IL-6 and TNF-α), associated to alleviating of aortic oxidative stress and integrity, highlighted the positive anti-atherogenic effect of STFE. CONCLUSION: Overall, the pleiotropic protective effect observed with S. terebinthifolius fruits might be related to the presence of various bioactive compounds.


Assuntos
Anacardiaceae/química , Inflamação/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Doenças Vasculares/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Aorta/patologia , Aterosclerose/induzido quimicamente , Aterosclerose/tratamento farmacológico , Glicemia/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Dieta Aterogênica/efeitos adversos , Frutas/química , Inflamação/metabolismo , Insulina/sangue , Lipídeos/sangue , Fígado/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Glicogênio Hepático/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Fenóis/análise , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia
14.
Drug Metab Dispos ; 49(1): 62-71, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33093018

RESUMO

Diet is an important factor for many diseases. Previous studies have demonstrated that several diets had remarkable effects on bile acid (BA) homeostasis, but no comprehensive information for both genders has been reported. Therefore, the current study characterized the nine most used laboratory animal diets fed to both genders of mice for a comparable evaluation of the topic. The results revealed that marked gender difference of BA homeostasis is ubiquitous in mice fed the various diets, and of the nine diets fed to mice, the atherogenic and calorie-restricted diets had the most marked effects on BA homeostasis, followed by the laboratory chow and essential fatty acid-deficient diets. More specifically, females had higher concentrations of total BAs in serum when fed six of the nine diets compared with male mice, and 26 of the 35 BA-related genes had marked gender difference in mice fed at least one diet. Although mice fed the calorie-restricted and atherogenic diets had increased BA, which was more pronounced in serum than liver, the intestinal farnesoid X nuclear receptor-fibroblast growth factor 15 axis changed in the opposite direction and resulted in different hepatic expression patterns of Cyp7a1 Compared with AIN-93M purified diet, higher hepatic expression of multidrug resistance-associated protein 3 was the only alteration in mice fed the laboratory chow diet. The other diets had little or no effect on BA concentrations in the liver and plasma or in the expression of BA-related genes. This study indicates that gender, the atherogenic diet, and the calorie-restricted diet have the most marked effects on BA homeostasis. SIGNIFICANCE STATEMENT: Previous evidence suggested that various diets have effect on bile acid (BA) homeostasis; however, it is not possible to directly compare these findings, as they are all from different studies. The current study was the first to systematically investigate the influence of the nine most used experimental mouse diets on BA homeostasis and potential mechanism in both genders of mice and indicates that gender, the atherogenic diet, and the calorie-restricted diet have the most marked effects on BA homeostasis, which will aid future investigations.


Assuntos
Ácidos e Sais Biliares/metabolismo , Restrição Calórica , Dieta Aterogênica , Regulação da Expressão Gênica/fisiologia , Fatores Sexuais , Transdução de Sinais/fisiologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Restrição Calórica/efeitos adversos , Restrição Calórica/métodos , Colesterol 7-alfa-Hidroxilase/metabolismo , Dieta/classificação , Dieta Aterogênica/efeitos adversos , Dieta Aterogênica/métodos , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Homeostase , Masculino , Camundongos , Receptores Citoplasmáticos e Nucleares/metabolismo
15.
Bull Exp Biol Med ; 170(2): 181-184, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33263842

RESUMO

Alimentary atherosclerosis is associated with a significant decrease in the content of phosphatidylcholine, the phospholipid that provides antioxidant protection, in the plasma membrane of liver cells, while the level of phosphatidic acid that initiates generation of superoxides, on the contrary, increases. The level of membrane phosphatidylserine, a target of the scavenger receptors, which initiates removal of damaged cells and modified lipoproteins from the circulation was also elevated. In the blood serum of rabbits receiving an atherogenic diet, the content of cardiolipin involved in the immune mechanisms of atherosclerosis development and a risk factor for thrombosis, sharply increased. The level of lysophosphatidylcholine that mediates initiation and progression of atherosclerosis increased. The content of phosphatidylinositol that is involved in the mechanisms protecting from exposure to excess cholesterol was significantly reduced. Treatment of alimentary atherosclerosis with "empty" phosphatidylcholine nanosomes eliminates the key factors initiating atherosclerosis development.


Assuntos
Aterosclerose/sangue , Membrana Celular/metabolismo , Fígado/metabolismo , Nanopartículas/química , Fosfatidilcolinas/química , Fosfolipídeos/química , Animais , Antioxidantes/química , Cardiolipinas/metabolismo , Dieta Aterogênica , Sistema Imunitário , Lipoproteínas/metabolismo , Lisofosfatidilcolinas/química , Coelhos , Fatores de Risco , Trombose/imunologia
16.
Molecules ; 25(22)2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33212852

RESUMO

Background: This study reports on the relative effects of administrating a cyanidin-3-O-glucoside-rich black rice fraction (BRF), a standardized wood sterol mixture (WS), and a combination of both to lower plasma and target tissue lipid concentrations in Wistar Kyoto (WKY) rats fed atherogenic diets. Methods: Male WKY (n = 40) rats were randomly divided into five groups, which included a nonatherogenic control diet and atherogenic diets that included a positive control and atherogenic diets supplemented with BRF or WS, respectively, and a combination of both BRF + WS. Plasma and target tissue liver, heart and aorta cholesterol, and triacylglycerides (TAG) content were also measured. Results: Rats fed atherogenic diets exhibited elevated hyperlipidemia compared to counterparts fed nonatherogenic diets (p < 0.001); this effect was mitigated by supplementing the atherogenic diets with BRF and WS, respectively (p < 0.05). Combining BRF with WS to enrich the supplement lowered cholesterol similar to the WS effect (p < 0.05) and lowered TAG characteristic to the BRF effect (p < 0.05). Conclusions: Rats fed diets containing BRF or WS effectively mitigate the hypercholesterolemia and elevated TAG induced by feeding an atherogenic diet. The benefit of adding BRF + WS together is relevant to the lipid parameter measured and is target tissue-specific.


Assuntos
Antocianinas/farmacologia , Dieta Aterogênica , Lipídeos/sangue , Oryza/química , Esteróis/farmacologia , Madeira/química , Animais , Peso Corporal/efeitos dos fármacos , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos Endogâmicos WKY , Esteróis/química , Aumento de Peso/efeitos dos fármacos
17.
Clin Transl Gastroenterol ; 11(9): e00234, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33094961

RESUMO

INTRODUCTION: Endoscopic bariatric and metabolic therapies can potentially reproduce similar gastric and small intestinal anatomic and physiologic manipulations as Roux-en-Y gastric bypass. This proof of concept animal study was aimed to assess the feasibility, safety, efficacy, and impact on gastrointestinal physiology of combined intragastric balloons (IGB) and duodenal-jejunal bypass liner (DJBL) for the treatment of obesity. METHODS: Five Ossabaw pigs were fed a high-calorie diet to develop obesity and were randomly assigned to receive IGB or DJBL in sequence. The weight gain rate was calculated. Fasting and postprandial blood samples were drawn before any intervention (serving as the baseline group) and 1 month after second device insertion (serving as the combination group) to measure gut neurohormonal changes and metabolic parameters. RESULTS: Four pigs successfully received a sequential device insertion. One pig developed duodenal sleeve prolapse that was spontaneously resolved. One pig was early terminated because of developing a central line infection. The rate of weight gain in the combination group (0.63 ± 1.3 kg/wk) was significantly lower than the baseline group (1.96 ± 2.17 kg/wk) and numerically lower than after insertion of the IGB (1.00 ± 1.40 kg/wk) or the DJBL (0.75 ± 2.27 kg/wk) alone. A trend of higher postprandial glucagon-like peptide-1 was observed in the combination group compared with the baseline group. DISCUSSION: A combination of IGB and DJBL is feasible and well tolerated. A strategy of sequential use of these devices might offer a synergistic approach that can enhance weight loss and metabolic outcomes.


Assuntos
Cirurgia Bariátrica/instrumentação , Duodeno/cirurgia , Balão Gástrico , Jejuno/cirurgia , Obesidade Mórbida/cirurgia , Anastomose em-Y de Roux/instrumentação , Anastomose em-Y de Roux/métodos , Animais , Cirurgia Bariátrica/métodos , Terapia Combinada/instrumentação , Terapia Combinada/métodos , Dieta Aterogênica/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Estudos de Viabilidade , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Obesidade Mórbida/sangue , Obesidade Mórbida/etiologia , Obesidade Mórbida/metabolismo , Período Pós-Prandial , Estudo de Prova de Conceito , Suínos , Porco Miniatura , Redução de Peso
18.
Int J Mol Sci ; 21(18)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957703

RESUMO

Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism. We aimed to investigate the effect of an FGF21 analogue (LY2405319) on the development of atherosclerosis and its associated parameters. ApoE-/- mice were fed an atherogenic diet for 14 weeks and were randomly assigned to control (saline) or FGF21 (0.1 mg/kg) treatment group (n = 10/group) for 5 weeks. Plaque size in the aortic arch/valve areas and cardiovascular risk markers were evaluated in blood and tissues. The effects of FGF21 on various atherogenesis-related pathways were also assessed. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the FGF21 group than in controls after treatment. FGF21 significantly decreased body weight and glucose concentrations, and increased circulating adiponectin levels. FGF21 treatment alleviated insulin resistance and decreased circulating concentrations of triglycerides, which were significantly correlated with plaque size. FGF21 treatment reduced lipid droplets in the liver and decreased fat cell size and inflammatory cell infiltration in the abdominal visceral fat compared with the control group. The monocyte chemoattractant protein-1 levels were decreased and ß-hydroxybutyrate levels were increased by FGF21 treatment. Uncoupling protein 1 expression in subcutaneous fat was greater and fat cell size in brown fat was smaller in the FGF21 group compared with controls. Administration of FGF21 showed anti-atherosclerotic effects in atherosclerosis-prone mice and exerted beneficial effects on critical atherosclerosis pathways. Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by FGF21 therapy.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Aterosclerose/metabolismo , Fatores de Crescimento de Fibroblastos/administração & dosagem , Metaboloma/efeitos dos fármacos , Placa Aterosclerótica/tratamento farmacológico , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/tratamento farmacológico , Peso Corporal/efeitos dos fármacos , Dieta Aterogênica , Modelos Animais de Doenças , Teste de Tolerância a Glucose , Gordura Intra-Abdominal/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/metabolismo , Proteína Desacopladora 1/metabolismo
19.
Am J Physiol Heart Circ Physiol ; 319(4): H814-H823, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32822214

RESUMO

Hypercholesterolemia- and atherosclerosis-caused vasomotor property dysfunction may be involved in many clinic manifestations of atherosclerosis, including angina, acute myocardial infarction, and sudden cardiac death. However, its underlying mechanism is not clear. The endothelial glycocalyx is a protective surface layer on the endothelial cells, serving as a molecular sieve, cell adhesion modulator, and mechanosensor for blood flow. In the present study, we demonstrated by confocal microscopy in Sprague-Dawley (SD) male rats fed a 12-wk high-cholesterol diet (HC) compared with the normal diet (NC) that the dimension of the endothelial glycocalyx reduced significantly in both the common carotid artery (2.89 ± 0.41 µm and 3.25 ± 0.44 µm, respectively) and the internal sinus region (2.35 ± 0.07 µm and 3.46 ± 0.86 µm, respectively). Furthermore, we showed by real-time PCR that this dimension modification of endothelial glycocalyx may be attributed to a significant downregulation of heparan sulfate proteoglycan (HSPG)-related genes, including syndecan-3, glypican-1, and EXT1, not resulting from an enhanced shedding of sulfated glycosaminoglycans (sGAGs) from the vessel wall to the plasma. Meanwhile, the mean contraction and relaxation forces of the common carotid artery with responses to norepinephrine (NE) and acetylcholine (ACh) decreased ~0.34- and 0.13-fold, respectively, accompanied by a lower level of nitric oxide (NO) release. These findings suggest that the atherogenic high cholesterol diet diminished endothelial glycocalyx and disturbed the local NO release, thus contributing to the impaired vasomotor properties of the vessel.NEW & NOTEWORTHY Twelve-week high-cholesterol (HC) diet reduces the thickness of the endothelial glycocalyx in Sprague-Dawley (SD) male rats, which is mainly attributed to a downregulation of heparan sulfate proteoglycan-related genes (syndecan-3, glypican-1, EXT1), not resulting from an enhanced shedding of sulfated glycosaminoglycans (sGAGs) into the plasma. HC-diminished glycocalyx may disturb its mechanotransduction of local shear stress, lower nitric oxide (NO) release, and impair vasomotor responses to norepinephrine (NE) and acetylcholine (ACh).


Assuntos
Artérias Carótidas/patologia , Doenças das Artérias Carótidas/patologia , Dieta Aterogênica , Células Endoteliais/patologia , Glicocálix/patologia , Vasoconstrição , Vasodilatação , Animais , Artérias Carótidas/metabolismo , Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/fisiopatologia , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Glicocálix/metabolismo , Glicosaminoglicanos/metabolismo , Masculino , Óxido Nítrico/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais
20.
Int J Mol Sci ; 21(13)2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32635347

RESUMO

Hemoglobin, heme and iron are implicated in the progression of atherosclerosis. Therefore, we investigated whether the hydrophobic fungal iron chelator siderophore, desferricoprogen (DFC) inhibits atherosclerosis. DFC reduced atherosclerotic plaque formation in ApoE-/- mice on an atherogenic diet. It lowered the plasma level of oxidized LDL (oxLDL) and inhibited lipid peroxidation in aortic roots. The elevated collagen/elastin content and enhanced expression of adhesion molecule VCAM-1 were decreased. DFC diminished oxidation of Low-density Lipoprotein (LDL) and plaque lipids catalyzed by heme or hemoglobin. Formation of foam cells, uptake of oxLDL by macrophages, upregulation of CD36 and increased expression of TNF-α were reduced by DFC in macrophages. TNF-triggered endothelial cell activation (vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecules (ICAMs), E-selectin) and increased adhesion of monocytes to endothelium were attenuated. The increased endothelial permeability and intracellular gap formation provoked by TNF-α was also prevented by DFC. DFC acted as a cytoprotectant in endothelial cells and macrophages challenged with a lethal dose of oxLDL and lowered the expression of stress-responsive heme oxygenase-1 as sublethal dose was employed. Saturation of desferrisiderophore with iron led to the loss of the beneficial effects. We demonstrated that DFC accumulated within the atheromas of the aorta in ApoE-/- mice. DFC represents a novel therapeutic approach to control the progression of atherosclerosis.


Assuntos
Dicetopiperazinas/farmacologia , Ácidos Hidroxâmicos/farmacologia , Placa Aterosclerótica/prevenção & controle , Sideróforos/farmacologia , Animais , Aorta/diagnóstico por imagem , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/patologia , Dieta Aterogênica , Dicetopiperazinas/farmacocinética , Modelos Animais de Doenças , Progressão da Doença , Células Espumosas/efeitos dos fármacos , Células Espumosas/patologia , Heme/metabolismo , Ácidos Hidroxâmicos/farmacocinética , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Neurospora crassa/química , Estresse Oxidativo/efeitos dos fármacos , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Tomografia por Emissão de Pósitrons , Sideróforos/farmacocinética
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