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2.
Vasc Health Risk Manag ; 16: 1-10, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021223

RESUMO

Icosapent ethyl is a highly purified formulation of eicosapentaenoic acid, a type of omega-3 fatty acid contained in fish oil. While omega-3 fatty acids have long been thought to have cardioprotective benefits, the Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT) has helped to establish icosapent ethyl as an evidence-based therapy for risk reduction of atherosclerotic cardiovascular disease (ASCVD). REDUCE-IT, however, was by no means an overnight success story. Close examination of the evidence shows that the trial was a culmination of many lessons learned from previous studies. The purpose of this manuscript is to review contemporary evidence of icosapent ethyl in ASCVD risk reduction and the clinical implication of this promising therapy.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Ácido Eicosapentaenoico/análogos & derivados , Animais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Suplementos Nutricionais/efeitos adversos , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/uso terapêutico , Medicina Baseada em Evidências , Humanos , Fatores de Proteção , Medição de Risco , Fatores de Risco
3.
Angiology ; 71(1): 10-16, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30966756

RESUMO

Cardiovascular disease (CVD) remains the major cause of death and disability worldwide, and residual risk after implementing all current therapies is still high. In this context, the latest (2016) European Cardiology Society/European Atherosclerosis Society guidelines recommend that triglyceride (TG)-lowering drugs should be used in high-risk patients with TGs levels >2.3 mmol/L (200 mg/dL), after lifestyle measures fail to lower them. After several neutral CVD outcome trials with n-3 fatty acids, the Reduction of Cardiovascular Events with EPA-Intervention Trial met its primary end point, that is, among patients with elevated TGs levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower in those who received 4 g of icosapent ethyl daily. In this review, we comment on the findings of previous and recently published randomized controlled CVD outcome trials assessing n-3 fatty acids supplementation. Both efficacy and safety, as well as future perspectives, are discussed.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Ácido Eicosapentaenoico/análogos & derivados , Ácidos Graxos Insaturados/uso terapêutico , Lipídeos/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Suplementos Nutricionais/efeitos adversos , Dislipidemias/sangue , Dislipidemias/epidemiologia , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos Insaturados/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
4.
Food Chem ; 308: 125607, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31677599

RESUMO

Lipid sources as alternatives to fish oil could alter the nutritional value and flavor quality of crab meat affecting consumer preferences. Herein, an 8-week nutritional trial was designed to investigate the effects of dietary lipid sources including fish oil (FO), krill oil (KO), palm oil, rapeseed oil, soybean oil and linseed oil on profiles of amino acids, fatty acids and volatiles in muscle of swimming crab (Portunus trituberculatus). Volatiles of crab muscle were characterized by headspace solid-phase microextraction and gas chromatography-tandem mass spectrometry. Results revealed that crabs fed FO and KO had significantly higher levels of protein, indispensable amino acids, eicosapentaenoic acid and docosahexaenoic acid in muscle. Principal component analysis and hierarchical cluster analysis demonstrated that muscle volatiles of crabs fed different dietary oils exhibited significant variations. Dietary FO and KO significantly increased the relative levels of 3-methylbutanal, heptanal, benzaldehyde and nonanal in muscle, which may produce more pleasant flavors.


Assuntos
Braquiúros/química , Aromatizantes/análise , Animais , Gorduras na Dieta/análise , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/análise , Ácidos Graxos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Estado Nutricional , Valor Nutritivo , Alimentos Marinhos/análise , Microextração em Fase Sólida , Natação , Paladar
5.
Prog Cardiovasc Dis ; 62(5): 401-405, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666183

RESUMO

The REDUCE-IT study found that patients at elevated risk for cardiovascular disease (CVD) who were already taking statins obtained a marked benefit by taking 4 g/d of eicosapentaenoic acid ethyl esters (icosapent ethyl, IPE; Vascepa) over about 5 years. Although approved for triglyceride (TG) lowering, IPE had only a modest TG-lowering effect in REDUCE-IT, largely because median TG levels were relatively low already. Hence the question of what mechanisms IPE might be working through is of great interest. At present, it appears that the best mechanistic candidates would be anti-platelet effects and/or anti-inflammatory effects. Whatever the cause, the powerful effects of IPE on CVD risk have renewed interest in the clinical utility of omega-3 fatty acids.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Ácido Eicosapentaenoico/análogos & derivados , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Guias de Prática Clínica como Assunto , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangue
6.
Prog Cardiovasc Dis ; 62(5): 395-400, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31715195

RESUMO

Statin therapy is effective in primary and secondary prevention, but substantial residual risk remains on statin treatment, especially among high risk and very high risk patients. Add-on therapy with ezetimibe and proprotein convertase subtilisin /kexin type 9 (PCSK9) inhibitors provides additional risk reduction through further reduction in low density lipoprotein cholesterol. Elevated triglycerides/triglyceride rich lipoproteins contribute to atherogenesis and to the residual risk on statin therapy. Addition of icosapent ethyl to statins has recently been shown to markedly lower risk of ASCVD events in patients with established atherosclerotic CVD (ASCVD) and high risk patients with type II diabetes mellitus. These data are discussed in the context of current guidelines and synthesized in a decision pathway to guide combination lipid-lowering therapy in patients at high ASCVD risk.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Ácido Eicosapentaenoico/análogos & derivados , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Serino Proteinase/uso terapêutico , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/uso terapêutico , Ezetimiba/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Guias de Prática Clínica como Assunto , Pró-Proteína Convertase 9/metabolismo , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento , Triglicerídeos/sangue
7.
BMC Vet Res ; 15(1): 324, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492181

RESUMO

BACKGROUND: Obesity in cats has been associated with alterations in adipokines including: adiponectin, interleukin-6 (IL6), and tumor necrosis factor-α (TNFα). Omega-3 polyunsaturated fatty acids have multiple beneficial effects on obesity-associated disorders, and therefore may alleviate these alterations. This study aimed to determine the effects of body condition, fat depot, troglitazone, and different fatty acids on secretion of adiponectin, IL6 and TNFα from adipose tissue of healthy cats. Subcutaneous and visceral adipose tissue samples were collected from 18 healthy intact female cats, and body condition score (Range 3-7/9) was determined. Concentrations of adiponectin were measured in mature adipocytes cultures and concentrations of IL6 and TNFα were measured in stromovascular cells cultures following treatment with control medium, troglitazone at 10 µM, eicosapentaenoic acid, arachidonic acid, or palmitic acid, at 25, 50, or 100 µM. RESULTS: Stromovascular cells of visceral origin secreted higher concentrations of IL6 than corresponding cells of subcutaneous origin (P = 0.003). Arachidonic acid treatment at 25, 50, and 100 µM increased IL6 secretion in subcutaneous (P = 0.045, P = 0.002, and P < 0.001, respectively) and visceral (P = 0.034, P = 0.001, and P < 0.001, respectively) stromovascular cells. Eicosapentaenoic acid treatment increased TNFα secretion in subcutaneous stromovascular cells at 25, 50, and 100 µM (P = 0.002, P = 0.001, and P = 0.015, respectively) and in visceral stromovascular cells at 50 µM (P < 0.001). No significant effect on medium adiponectin concentration was observed following troglitazone treatment (P = 0.4) or fatty acids treatments at 25 (P = 0.2), 50 (P = 0.8), or 100 (P = 0.7) µM. Body condition score did not have significant effects on medium concentrations of adiponectin (P = 0.4), IL6 (P = 0.1), or TNFα (P = 0.8). CONCLUSIONS: This study demonstrated higher basal secretion of IL6 from visceral compared to subcutaneous adipose tissue, a stimulatory effect of arachidonic acid on secretion of IL6 and a stimulatory effect of eicosapentaenoic acid on TNFα from feline adipose tissue.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Tecido Adiposo/metabolismo , Animais , Ácido Araquidônico/metabolismo , Constituição Corporal , Gatos , Células Cultivadas , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Feminino , Interleucina-6/metabolismo , Ácido Palmítico/metabolismo , Troglitazona/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
8.
Meat Sci ; 158: 107878, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401371

RESUMO

We investigated the fatty acid (FA) composition, oxidative biomarkers and quality traits of chilled beef. Specifically, striploin portions were held in vacuo and chilled (~ 1.5 °C) for up to 12 weeks, and analysed dependent on their assigned chilled storage period (0, 2, 5, 8, 10 and 12 weeks). There were no practical effects observed on beef FA composition as a result of chilled storage - including several polyunsaturated FA (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Intramuscular fat content was found to have a covariate effect, but only for saturated FA and monounsaturated FA. Vitamin E and thiobarbituric acid reactive substances were unchanged. Furthermore, improvements to shear force and particle size were evident at 2 weeks and thereafter, no further variation was evident. These findings suggest that beef produced to be healthier based on the EPA, DHA and PUFA content will remain so, for up to 12 weeks. Likewise, beef quality will be preserved across this same period.


Assuntos
Ácidos Graxos/análise , Carne Vermelha/normas , Refrigeração , Animais , Austrália , Biomarcadores , Bovinos , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análogos & derivados , Armazenamento de Alimentos/métodos , Oxirredução , Carne Vermelha/análise , Resistência ao Cisalhamento , Vácuo
9.
J Endod ; 45(9): 1126-1134.e1, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31353056

RESUMO

INTRODUCTION: Timely resolution of pulp inflammation is a prerequisite for the healing of inflamed dental pulp. Stromal cells, particularly fibroblasts, play a critical role in the inflammation resolution process. Resolvin E1 (RvE1) is a lipid-derived endogenous proresolution molecule that mediates this resolution process. In the present study, we investigated the effects of RvE1 on dental fibroblasts during the pathogenesis of pulpitis. METHODS: The pulp tissues in maxillary incisors of male Sprague-Dawley rats (N = 50) were exposed to the oral environment for 0, 9, 24, and 48 hours, after which they were treated with RvE1 or its vehicle. The inflammatory changes after 24 hours were assessed using hematoxylin-eosin staining, immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction. Chemerin receptor 23 (ChemR23) expression in rat pulp tissues and human dental fibroblasts was detected by immunofluorescence, Western blot analysis, and quantitative polymerase chain reaction. Finally, small interfering RNA-based knockdown studies were performed to evaluate the effects of RvE1 inhibition on proinflammatory genes and nuclear factor kappa B signaling of human dental pulp fibroblasts. RESULTS: Early treatment (within 24 hours after pulp exposure) with RvE1 promoted a decline in the number of inflammatory cells and gene expression of proinflammatory cytokines. Moreover, it reduced ChemR23 expression in the fibroblastlike cells of inflamed pulp tissues. In vitro, ChemR23 was widely expressed in human dental fibroblasts. RvE1 significantly suppressed cytokine production by fibroblasts, with down-regulation of the nuclear translocation of nuclear factor kappa B p65 in these cells. Knockdown of ChemR23 almost abolished the anti-inflammatory effect of RvE1. CONCLUSIONS: RvE1 can suppress the activation of dental pulp fibroblasts in a ChemR23-dependent manner and inhibit inflammation in the relevant early stages of pulpitis.


Assuntos
Ácido Eicosapentaenoico/análogos & derivados , Pulpite , Animais , Quimiocinas , Polpa Dentária , Ácido Eicosapentaenoico/farmacologia , Fibroblastos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Pulpite/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
10.
Am J Cardiol ; 124(5): 696-701, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31277790

RESUMO

Icosapent ethyl is pure prescription eicosapentaenoic acid approved at 4 g/day as an adjunct to diet to reduce triglycerides (TG) in adults with TG ≥500 mg/dl. Elevated high-sensitivity C-reactive protein (hsCRP) is associated with increased cardiovascular risk. The 12-week ANCHOR study randomized 702 statin-treated patients at increased cardiovascular risk with TG 200 to 499 mg/dl despite low-density lipoprotein cholesterol (LDL-C) control (40 to 99 mg/dl). This post hoc analysis assessed 246 ANCHOR patients with baseline hsCRP ≥ 2.0 mg/L randomized to icosapent ethyl 4 g/day (n = 126; approved dose) or placebo (n = 120). Without increasing LDL-C, icosapent ethyl significantly reduced median TG (-20%; p < 0.0001), non-high-density lipoprotein cholesterol (-12.3%; p < 0.0001), total cholesterol (-11.1%; p < 0.0001), high-density lipoprotein cholesterol (-5.2%; p = 0.0042), very LDL-C (-21.0%; p < 0.0001), very low-density lipoprotein TG (-22.9%; p < 0.0001), remnant lipoprotein cholesterol (-23.0%; p = 0.0125), apolipoprotein B (-7.4%; p = 0.0021), apolipoprotein C-III (-16%; p < 0.0001), oxidized LDL (-13.7%; p = 0.0020), lipoprotein-associated phospholipase A2 (-19.6%; p < 0.0001), and hsCRP (-17.9%; p = 0.0213) versus placebo, while interleukin-6 and intercellular adhesion molecule-1 were not significantly changed. Eicosapentaenoic acid increased with icosapent ethyl 4 g/day +637% in plasma and +632% in red blood cells versus placebo (both p < 0.0001). Icosapent ethyl exhibited a safety profile similar to placebo. In conclusion, in statin-treated patients with hsCRP ≥ 2.0 mg/L and TG 200 to 499 mg/dl at baseline, icosapent ethyl 4 g/day significantly and safely reduced TG and other atherogenic and inflammatory parameters without increasing LDL-C versus placebo.


Assuntos
Proteína C-Reativa/metabolismo , Substituição de Medicamentos/métodos , Ácido Eicosapentaenoico/análogos & derivados , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Adulto , Idoso , Apolipoproteína C-III/sangue , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , LDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Ácido Eicosapentaenoico/uso terapêutico , Feminino , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos
11.
J Sci Food Agric ; 99(13): 6066-6075, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228262

RESUMO

BACKGROUND: Isochrysis sp. is a marine microalga, rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The potential use of its biomass as an alternative source of polyunsaturated fatty acids (PUFAs) has not been studied in animal models. Male albino Wistar rats were divided into three groups and treated for 28 days. The rats were fed with (1) standard chow (control group), (2) microalgal biomass rich in EPA and DHA along with standard chow (microalga group), and (3) fish oil that contains equivalent amounts of EPA and DHA along with standard chow (fish oil group). After intervention, biochemical indices, histopathological indices, relative mRNA expression of PUFA genes, antioxidant genes, inflammatory markers, and the fatty acid profile of major tissues were studied. RESULTS: Animals treated with microalgal biomass showed significantly increased serum HDL levels (P < 0.05) and reduced oxidative stress markers with a concomitant decrease in urea and creatinine levels. Oral supplementation of microalgal biomass did not show any toxicity or damage in any major organs. The mRNA expression of PUFA genes was significantly downregulated (P < 0.05) and antioxidant genes were upregulated. Furthermore, the mRNA expression of pro-inflammatory markers was significantly downregulated (P < 0.05) and anti-inflammatory markers were upregulated. Oral supplementation of microalgal biomass improved DHA status in brain and liver. CONCLUSION: The present study demonstrated that Isochrysis sp. can be used as a safe, alternative food supplement for ω-3 fatty acids. © 2019 Society of Chemical Industry.


Assuntos
Antioxidantes/metabolismo , Suplementos Nutricionais/análise , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Haptófitas/química , Lipídeos/sangue , Microalgas/química , Animais , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Insaturados/metabolismo , Expressão Gênica , Haptófitas/crescimento & desenvolvimento , Haptófitas/metabolismo , Fígado/metabolismo , Masculino , Microalgas/crescimento & desenvolvimento , Microalgas/metabolismo , Ratos , Ratos Wistar
12.
Food Chem ; 297: 124937, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253257

RESUMO

Diatoms are a major group of high omega 3-fatty acid producing algae that play a key role in global climate change and ecosystem function. Phaeodactylum tricornutum is one of only two diatoms whose genomes have been completely sequenced, leading to metabolic engineering of high eicosapentaenoic acid producing strains. Based on its rapid growth, high lipid content, and especially omega-3 long chain unsaturated fatty acids, P. tricornutum exhibits a large commercial potential. However, until now, it is predominately produced as feed for the aquaculture industry, rather than food supplement. This review compares the change of P. tricornutum lipid composition under different treatments, and identifies suitable lipid induction, cultivation and harvesting methods for industry adoption. If produced in a biorefinery setting, P. tricornutum has strong potential for value generation from human health products (omega-3-rich oil and high-value protein) with cost estimates of AU$6.14 per kg dry weight and AU$20.47 for omega-3-rich oil.


Assuntos
Diatomáceas/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Lipídeos/química , Dióxido de Carbono/química , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Indústria Alimentícia , Concentração de Íons de Hidrogênio
13.
Food Funct ; 10(7): 3955-3964, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31199413

RESUMO

Sea cucumber saponins (SCS) exhibit a significant effect on ameliorating glucose and lipid disorders by inhibiting fatty acid biosynthesis; however, high cytotoxicity and hemolytic activity limit their application. Eicosapentaenoic acid-enriched phospholipids (EPA-PL) significantly ameliorate insulin resistance and elevate the level of hepatic lipolysis, which may have a synergistic effect with SCS in alleviating obesity-related insulin resistance via multiple mechanisms. In the present study, high-fat diet-induced male C57BL/6J mice with obesity-related insulin resistance were used to evaluate the synergistic effect of SCS and EPA-PL on alleviating the insulin resistance. Results show that the combination of SCS and EPA-PL at a half dose exhibited a significant improvement on glucose intolerance and systematic insulin sensitivity than SCS or EPA-PL alone. Moreover, the half dose-combination remarkably inhibited the macrophage infiltration (F4/80) to white adipose tissue (WAT) and significantly down-regulated the level of MCP1, TNF-α and IL-6 compared with SCS and EPA-PL alone. Consequently, the combined administration not only decreased hepatic gluconeogenesis and increased hepatic glycogen synthesis (P < 0.05), but also stimulated the glucose uptake in WAT and muscle (P < 0.05). Nevertheless, neither SCS or EPA-PL alone exhibited any effect on the glucose uptake. The combination of SCS and EPA-PL contributed to a synergistic effect on alleviating the obesity-related insulin resistance due to the amelioration of an inflammation-centric peripheral insulin response.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Ácido Eicosapentaenoico/análogos & derivados , Resistência à Insulina , Obesidade/tratamento farmacológico , Fosfolipídeos/administração & dosagem , Saponinas/administração & dosagem , Pepinos-do-Mar/química , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Sinergismo Farmacológico , Quimioterapia Combinada , Ácido Eicosapentaenoico/administração & dosagem , Glucose/metabolismo , Intolerância à Glucose/tratamento farmacológico , Teste de Tolerância a Glucose , Insulina , Interleucina-6/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Lipólise/efeitos dos fármacos , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Fator de Necrose Tumoral alfa/metabolismo
14.
Environ Sci Pollut Res Int ; 26(22): 22197-22208, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148000

RESUMO

Acrylamide (ACR), a ubiquitous agent, has various chemical and industrial applications, and it is found in backed or fried carbohydrate-rich food. It has been related to multiple toxicological effects, and it causes high cytotoxicity through oxidative stress. The present study aimed to investigate the potential effect of ACR toxicity administered at different concentrations (5, 10, and 20 mg/L), during 5 days, in order to evaluate the fatty acid (FA) composition and redox state in the digestive gland of Mactra corallina. The results showed, in ACR-treated clams, a significant increase in malondialdehyde, hydrogen peroxide, protein carbonyl, and metallothionein levels, as well as an alteration of the enzymatic (superoxide dismutase, glutathione peroxidase, and catalase) and non-enzymatic (reduced glutathione and ascorbic acid) antioxidant status. However, acetylcholinesterase activity was inhibited in a concentration-dependent manner. In our experiment, the n-3 (Omega-3) and n-6 (Omega-6) polyunsaturated fatty acid levels were significantly changed in all ACR-treated groups. A decrease in eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA) was observed in 10-mg/L and 20-mg/L ACR-treated groups. Nevertheless, arachidonic acid (C20:4n-6, ARA) and its precursor linoleic acid (C18:2n-6, LA) were increased. Besides oxidative stress parameters, FA composition may be an additional tool for assessing ACR contamination.


Assuntos
Acrilamida/farmacologia , Bivalves/metabolismo , Digestão/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos/metabolismo , Superóxido Dismutase/metabolismo , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Ácido Araquidônico/química , Bivalves/química , Catalase/metabolismo , Ácidos Docosa-Hexaenoicos/química , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/química , Glutationa/metabolismo , Ácido Linoleico/química , Ácido Linoleico/farmacologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos
15.
BMC Pulm Med ; 19(1): 97, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31122230

RESUMO

BACKGROUND: Omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and derivatives, play a key role in the resolution of inflammation. Higher intake has been linked to decreased morbidity in several diseases, though effects on respiratory diseases like COPD are understudied. METHODS: The National Health and Nutrition Examination Survey (NHANES), with a focus on dietary assessment, provides a unique opportunity to explore relationships between omega-3 intake and morbidity in respiratory diseases marked by inflammation in the United States (US) population. We investigated relationships between ALA or EPA + DHA intake and respiratory symptoms among US adults with COPD, as well as variation in relationships based on personal characteristics or exposures. RESULTS: Of 878 participants, mean age was 60.6 years, 48% were current smokers, and 68% completed high school. Omega-3 intake was, 1.71 ± 0.89 g (ALA), and 0.11 ± 0.21 g (EPA + DHA). Logistic regression models, adjusting for age, gender, race, body mass index, FEV1, education, smoking status, pack-years, total caloric intake, and omega-6 (linoleic acid, LA) intake demonstrated no primary associations between omega-3 intake and respiratory symptoms. Interaction terms were used to determine potential modification of relationships by personal characteristics (race, gender, education) or exposures (LA intake, smoking status), demonstrating that at lower levels of LA intake, increasing ALA intake was associated with reduced odds of chronic cough (pint = 0.015) and wheeze (pint = 0.037). EPA + DHA, but not ALA, was associated with reduced symptoms only among current smokers who did not complete high school. CONCLUSIONS: Individual factors should be taken into consideration when studying the association of fatty acid intake on respiratory diseases, as differential responses may reveal susceptible subgroups.


Assuntos
Tosse/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Sons Respiratórios/efeitos dos fármacos , Idoso , Tosse/epidemiologia , Estudos Transversais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/análogos & derivados , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Testes de Função Respiratória , Estados Unidos , Ácido alfa-Linoleico/administração & dosagem
16.
Expert Opin Pharmacother ; 20(10): 1221-1225, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31038369

RESUMO

Introduction: Hypertriglyceridemia is common and increases cardiovascular risk. Fish oil decreases triglyceride levels, but also increases low-density lipoprotein (LDL) cholesterol, which may negate any cardiovascular benefits. EPA, a component of fish oil, reduces triglyceride levels without increasing LDL cholesterol. Areas covered: Two forms of purified EPA ethyl ester are available on prescription. This review considers the clinical trials of these purified esters to treat hypertriglyceridemia and shows that the EPA ethyl esters reduce triglyceride levels and reduce cardiovascular events. Expert opinion: To date, the effects of the purified EPA ethyl esters on cardiovascular events have only been tested in subjects taking statins. With statin treatment, if hypertriglyceridemia persists, it may be worthwhile considering adding an EPA ethyl ester. However, as the fibrates reduce the triglyceride levels by similar amounts to the EPA ethyl esters, while increasing the levels of HDL cholesterol, they are an alternative to EPA ethyl esters in combination with statins. As the proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors reduce triglycerides to a similar extent to the EPA ethyl ester, while reducing LDL cholesterol levels to a greater extent than the statins, they should be considered as an alternative to the statin/EPA ethyl ester combination.


Assuntos
Ácido Eicosapentaenoico/análogos & derivados , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipertrigliceridemia/tratamento farmacológico , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Ácido Eicosapentaenoico/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Triglicerídeos/sangue
17.
J Anim Sci ; 97(6): 2631-2643, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31073599

RESUMO

Omega-3 long chain fatty acids have a positive impact on production. When consumed during late gestation, it might have fetal programming effects on the fetus, which will have lifelong impacts on development and production. The objectives of the present study were to evaluate the effect of increasing doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the diet of ewes in the last third of gestation on their body weight (BW), subcutaneous adipose tissue relative mRNA abundance of genes associated with adipose tissue metabolism, and growth performance and plasma metabolites and hormones of their offspring during the finishing phase. Ewes (n = 72) were blocked by BW and allotted to pens (8 per treatment) with 3 ewes per pen. Ewes were supplemented with an EPA and DHA source (Strata G113) at concentrations of 0, 1, or 2% of dry matter intake during the last 50 d of gestation. At lambing, all ewes were penned together and offered the same diet. After weaning at 60 d of age, lambs were blocked by BW and sex and fed for 56 d. All lambs were fed the same pellet diet (61.09% ground corn, 24.08% soy hulls, 11.09% soybean meal, 1.48% Ca salt of palm oil, and 2.26% mixed mineral vitamin), and were weighed every 14 d until the end of the trial. Blood samples were collected on the weight sampling days. Dry matter intake and refusals were weighed daily. Data were analyzed as a randomized complete block design with repeated measurements (SAS 9.4). Polynomial contrast (linear-L and quadratic-Q) was used for mean separation. There were no differences in ewe body condition score, milk production, milk fat, or milk protein, but there was a trend for increased (L, P = 0.06) lactose concentration, and also differences in DGAT1 (L, P = 0.04), Δ5-desaturase (Q, P = 0.06) and Δ6-desaturase (Q, P = 0.07), PPARα (Q, P = 0.03), ELOVL2 and 5 (Q, P < 0.07), FABP4 (Q, P = 0.04), FATP1 (Q, P = 0.06), leptin (Q, P = 0.02), and resistin (L, P = 0.05). Feeding pregnant ewes an increased amount of EPA and DHA in late gestation increased final BW (L, P = 0.01), ADG (L, P = 0.04; Q, P = 0.01), DMI (Q, P ≤ 0.01), plasma glucose concentration (L, P = 0.04), and trended to decrease ghrelin concentrations (L, P = 0.07) in offspring during the finishing period. Dam supplementation did not affect G:F, nor plasma NEFA concentration (P ≥ 0.53) of lambs. Therefore, increasing supplementation of EPA and DHA in pregnant ewes has an impact on offspring performance, increasing DMI, ADG, and BW.


Assuntos
Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/análogos & derivados , Grelina/análise , Ovinos/fisiologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Dieta/veterinária , Ácido Eicosapentaenoico/farmacologia , Feminino , Gravidez , Desmame
18.
J Anim Sci ; 97(7): 3071-3088, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31063536

RESUMO

The objective of this study was to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation to ewes during late gestation on finishing lamb liver and adipose tissue fatty acid (FA) profile and gene expression. Lambs born from ewes supplemented with Ca salts of EPA + DHA, or palm FA distillate (PFAD) high in palmitic and oleic acid at 0.39% DM during the last 50 d of gestation were used. Lambs were weaned at 61 d of age and adapted to a high concentrate diet for 1.5 mo. After adaptation, 74 lambs (28 pens) were blocked by sex and BW and used in a 2 × 2 factorial arrangement of treatments using the factors of dam supplementation (DS) and lamb supplementation (LS) of Ca salts of EPA + DHA or PFAD at 1.48% DM. Lambs were slaughtered after 42 d and liver and adipose tissue collected for FA and gene expression analysis. Liver concentrations of EPA and DHA were greater (P < 0.01) with LS of EPA + DHA vs. PFAD during the finishing period. In adipose tissue, a lamb × dam interaction was observed for EPA (P = 0.02) and DHA (P = 0.04); LS of EPA + DHA increased EPA and DHA, but the increase was greatest in lambs born from ewes supplemented with PFAD. No lamb × dam treatment interactions were observed for gene expression in liver tissue (P > 0.10). Hepatic mRNA abundance of hormone-sensitive lipase (HSL; P = 0.01) was greater in lambs born from EPA + DHA ewes vs. lambs from PFAD ewes. mRNA expression of stearoyl-CoA desaturase (P < 0.01), fatty acid synthase (P = 0.01), Δ5-desaturase (P < 0.01), and Δ6-desaturase (P < 0.01) were decreased in liver of EPA + DHA lambs. A significant lamb × dam diet interaction was observed for elongation of very long chain fatty acid 2 in adipose tissue (P = 0.01); lambs supplemented with the same FA as their dams had lower expression. Expression of HSL tended (P = 0.08) to be decreased in adipose of EPA + DHA lambs born from EPA + DHA ewes. The changes in mRNA expression suggest that lipogenesis decreased, and lipolysis increased in lamb liver with EPA + DHA vs. PFAD supplementation during the finishing period. In adipose tissue, changes suggest that lipogenesis decreased in lambs born from EPA + DHA supplemented dams and supplemented with EPA + DHA during the finishing period. In addition, these results suggest an interaction between supplementation of FA to dams during late gestation on lamb response of adipose tissue, but not liver, to FA supplementation during the finishing period.


Assuntos
Suplementos Nutricionais/análise , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos/farmacologia , Ovinos/fisiologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Ração Animal/análise , Animais , Cálcio/farmacologia , Dieta/veterinária , Ácido Eicosapentaenoico/análogos & derivados , Ácidos Graxos não Esterificados/metabolismo , Feminino , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Parto/efeitos dos fármacos , Gravidez , Distribuição Aleatória , Ovinos/genética , Desmame
19.
J Exp Clin Cancer Res ; 38(1): 187, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072371

RESUMO

BACKGROUND: Current prognostic tools and targeted therapeutic approaches have limited value for metastatic triple negative breast cancer (TNBC). Building upon current knowledge, we hypothesized that epoxyeicosatrienoic acids (EETs) and related CYP450 epoxygenases may have differential roles in breast cancer signaling, and better understanding of which may uncover potential directions for molecular stratification and personalized therapy for TNBC patients. METHODS: We analyzed the oxylipin metabolome of paired tumors and adjacent normal mammary tissues from patients with pathologically confirmed breast cancer (N = 62). We used multivariate statistical analysis to identify important metabolite contributors and to determine the predictive power of tumor tissue metabolite clustering. In vitro functional assays using a panel of breast cancer cell lines were carried out to further confirm the crucial roles of endogenous and exogenous EETs in the metastasis transformation of TNBC cells. Deregulation of associated downstream signaling networks associated with EETs/CYPs was established using transcriptomics datasets from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Comparative TNBC proteomics using the same tissue specimens subjected to oxylipin metabolomics analysis was used as validation set. RESULTS: Metabolite-by-metabolite comparison, tumor immunoreactivity, and gene expression analyses showed that CYP epoxygenases and arachidonic acid-epoxygenation products, EET metabolites, are strongly associated with TNBC metastasis. Notably, all the 4 EET isomers (5,6-, 8,9-, 11,12-, and 14,15-EET) was observed to profoundly drive the metastasis transformation of mesenchymal-like TNBC cells among the TNBC (basal- and mesenchymal-like), HER2-overexpressing and luminal breast cancer cell lines examined. Our pathway analysis revealed that, in hormone-positive breast cancer subtype, CYP epoxygenase overexpression is more related to immune cell-associated signaling, while EET-mediated Myc, Ras, MAPK, EGFR, HIF-1α, and NOD1/2 signaling are the molecular vulnerabilities of metastatic CYP epoxygenase-overexpressing TNBC tumors. CONCLUSIONS: This study suggests that categorizing breast tumors according to their EET metabolite ratio classifiers and CYP epoxygenase profiles may be useful for prognostic and therapeutic assessment. Modulation of CYP epoxygenase and EET-mediated signaling networks may offer an effective approach for personalized treatment of breast cancer, and may be an effective intervention option for metastatic TNBC patients.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Ácido Eicosapentaenoico/genética , Metaboloma/genética , Oxilipinas/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Ácido Araquidônico/genética , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Feminino , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Transdução de Sinais/genética , Nanomedicina Teranóstica , Neoplasias de Mama Triplo Negativas/patologia
20.
Nutrients ; 11(4)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022842

RESUMO

In this study, two capsaicin analogues, N-eicosapentaenoyl vanillylamine (EPVA) and N-docosahexaenoyl vanillylamine (DHVA), were enzymatically synthesized from their corresponding n-3 long chain polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both dietary relevant components. The compounds significantly reduced the production of some lipopolysaccharide (LPS)-induced inflammatory mediators, including nitric oxide (NO), macrophage-inflammatory protein-3α (CCL20) and monocyte chemoattractant protein-1 (MCP-1 or CCL2), by RAW264.7 macrophages. Next to this, only EPVA increased insulin secretion by pancreatic INS-1 832/13 ß-cells, while raising intracellular Ca2+ and ATP concentrations. This suggests that the stimulation of insulin release occurs through an increase in the intracellular ATP/ADP ratio in the first phase, while is calcium-mediated in the second phase. Although it is not yet known whether EPVA is endogenously produced, its potential therapeutic value for diabetes treatment merits further investigation.


Assuntos
Capsaicina/análogos & derivados , Capsaicina/farmacologia , Ácidos Docosa-Hexaenoicos/análogos & derivados , Ácido Eicosapentaenoico/análogos & derivados , Ácidos Graxos Ômega-3/química , Inflamação/metabolismo , Insulina/metabolismo , Macrófagos/efeitos dos fármacos , Animais , Cálcio/metabolismo , Capsaicina/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/síntese química , Ácidos Docosa-Hexaenoicos/química , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/síntese química , Ácido Eicosapentaenoico/química , Ácido Eicosapentaenoico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Células RAW 264.7 , Ratos
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