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1.
Medicine (Baltimore) ; 99(35): e21955, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871944

RESUMO

BACKGROUND: Hypertension is a clinically common cardiovascular disease, resulting in many complications. Omega-3 might be beneficial in lowering blood pressure. This protocol will be performed to evaluate the effects of omega-3 on blood pressure in hypertensive patients. METHODS: We will search both the electronical databases and paper-published journals. Endnote software will be used to complete study screening and data extraction by 2 reviewers independently. Review Manager software will be used to synthesize the data. The primary outcomes are systolic blood pressure and diastolic blood pressure. Secondary outcome is the adverse effects. RESULTS: The results of this study will propose a trustworthy evidence to evaluate the effects of omega-3 on blood pressure of hypertensive patients. CONCLUSION: The conclusion of our systematic review will reply whether omega-3 is an effectual intervention to lower blood pressure of hypertensive patients. ETHICS: This review does not require ethical approval because all of the data analyzed in this review have been published. REGISTRATION NUMBER: INPLASY202070103 (DOI number: 10.37766/inplasy2020.7.0103).


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Ácidos Graxos Ômega-3/uso terapêutico , Hipertensão/prevenção & controle , Ácidos Graxos Ômega-3/farmacologia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
2.
Adv Exp Med Biol ; 1259: 125-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578175

RESUMO

Patients with cancer frequently overexpress inflammatory cytokines with an associated neutrophilia both of which may be downregulated by diets with high omega-3 polyunsaturated fatty acids (ω-3 PUFA). The anti-inflammatory activity of dietary ω-3 PUFA has been suggested to have anticancer properties and to improve survival of cancer patients. Currently, the majority of dietary research efforts do not differentiate between obesity and dietary fatty acid consumption as mediators of inflammatory cell expansion and tumor microenvironmental infiltration, initiation, and progression. In this chapter, we discuss the relationships between dietary lipids, inflammation, neoplasia and strategies to regulate these relationships. We posit that dietary composition, notably the ratio of ω-3 vs. ω-6 PUFA, regulates tumor initiation and progression and the frequency and sites of metastasis that, together, impact overall survival (OS). We focus on three broad topics: first, the role of dietary lipids in chronic inflammation and tumor initiation, progression, and regression; second, lipid mediators linking inflammation and cancer; and third, dietary lipid regulation of murine and human tumor initiation, progression, and metastasis.


Assuntos
Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Neoplasias , Microambiente Tumoral/efeitos dos fármacos , Animais , Dieta , Ácidos Graxos Ômega-6/farmacologia , Humanos , Inflamação/dietoterapia , Inflamação/patologia , Neoplasias/dietoterapia , Neoplasias/patologia
3.
PLoS One ; 15(5): e0233183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413078

RESUMO

Lupus is a debilitating multi-organ autoimmune disease clinically typified by periods of flare and remission. Exposing lupus-prone female NZBWF1 mice to crystalline silica (cSiO2), a known human autoimmune trigger, mimics flaring by inducing interferon-related gene (IRG) expression, inflammation, ectopic lymphoid structure (ELS) development, and autoantibody production in the lung that collectively accelerate glomerulonephritis. cSiO2-triggered flaring in this model can be prevented by supplementing mouse diet with the ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). A limitation of previous studies was the use of purified diet that, although optimized for rodent health, does not reflect the high American intake of saturated fatty acid (SFA), ω-6 PUFAs, and total fat. To address this, we employed here a modified Total Western Diet (mTWD) emulating the 50th percentile U.S. macronutrient distribution to discern how DHA supplementation and/or SFA and ω-6 reduction influences cSiO2-triggered lupus flaring in female NZBWF1 mice. Six-week-old mice were fed isocaloric experimental diets for 2 wks, intranasally instilled with cSiO2 or saline vehicle weekly for 4 wks, and tissues assessed for lupus endpoints 11 wks following cSiO2 instillation. In mice fed basal mTWD, cSiO2 induced robust IRG expression, proinflammatory cytokine and chemokine elevation, leukocyte infiltration, ELS neogenesis, and autoantibody production in the lung, as well as early kidney nephritis onset compared to vehicle-treated mice fed mTWD. Consumption of mTWD containing DHA at the caloric equivalent to a human dose of 5 g/day dramatically suppressed induction of all lupus-associated endpoints. While decreasing SFA and ω-6 in mTWD modestly inhibited some disease markers, DHA addition to this diet was required for maximal protection against lupus development. Taken together, DHA supplementation at a translationally relevant dose was highly effective in preventing cSiO2-triggered lupus flaring in NZBWF1 mice, even against the background of a typical Western diet.


Assuntos
Dieta Ocidental/efeitos adversos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Lúpus Eritematoso Sistêmico/dietoterapia , Dióxido de Silício/toxicidade , Animais , Linfócitos B/imunologia , Citocinas/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Graxos/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Feminino , Glomerulonefrite/dietoterapia , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Inflamação/imunologia , Interferon gama/metabolismo , Rim/metabolismo , Rim/patologia , Pulmão/metabolismo , Pulmão/patologia , Lúpus Eritematoso Sistêmico/induzido quimicamente , Camundongos , Linfócitos T/imunologia
4.
Arch Biochem Biophys ; 687: 108387, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32348741

RESUMO

Although acetaminophen (APAP) is a commonly used analgesic antipyretic drug, hepatotoxicity and nephrotoxicity are common after the overdose. The main mechanism of APAP toxicity is oxidative stress based. Stress may induce the production of heme oxygenase 1 (HO)-1 which is regulated by interleukin (IL)-10 and inhibit the production of tumor necrosis factor-alpha (TNF-α). HO-1 expression is further regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) and the transcription factor BTB and CNC homology 1 (BACH1). Drug-induced toxicity can be relieved by several natural products, which are preferred due to their dietary nature and less adverse reactions. Of these natural products, omega-3 (ω-3) fatty acids are known for anti-inflammatory and antioxidant actions. However, effects of ω-3fatty acids on APAP-induced hepatic and renal toxicity are not well addressed. We designed this study to test the potential protecting actions of ω-3 fatty acids (270 mg/kg Eicosapentaenoic acid and 180 mg/kg docosahexaenoic acid, orally, for 7 days) in hepatotoxicity and nephrotoxicity induced by APAP (2 g/kg, once orally on day 7) in rats. Moreover, we focused on the molecular mechanism underlying APAP hepatotoxicity and nephrotoxicity. Pre-treatment with ω-3 fatty acids enhanced liver and kidney functions indicated by decreased serum aminotransferases activities and serum creatinine and urea concentrations. These results were further confirmed by histopathological examination. Moreover, ω-3 fatty acids showed antioxidant properties confirmed by decreased malondialdehyde level and increased total antioxidant capacity. Antioxidant Nrf2, its regulators (HO-1 and BACH1) and the anti-inflammatory cytokine (IL-10) were up-regulated by APAP administration as a compensatory mechanism and they were normalized by ω-3 fatty acids. ω-3 fatty acids showed anti-inflammatory actions through down-regulating nuclear factor kappa B (NF-ĸB) and its downstream TNF-α. Moreover, Western blot analysis showed that ω-3 fatty acids promoted Nrf2 translocation to the nucleus; BACH1 exit from the nucleus and inhibited NF-ĸB nuclear translocation. These findings suggested the protecting actions of ω-3 fatty acids against APAP-induced hepatic and renal toxicity through regulation of antioxidant Nrf2 and inflammatory NF-ĸB pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Ácidos Graxos Ômega-3/farmacologia , Nefropatias/prevenção & controle , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Acetaminofen , Animais , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Núcleo Celular/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Regulação para Baixo , Heme Oxigenase (Desciclizante)/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Fígado/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Proteínas Repressoras/metabolismo , Fator de Crescimento Transformador alfa/metabolismo
5.
Clin Hemorheol Microcirc ; 75(3): 303-311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280083

RESUMO

BACKGROUND: An adequate erythrocyte function is vital for tissue oxygenation and wound healing. The erythrocyte membrane phospholipid composition plays an important role in erythrocyte function and administration of omega-3 fatty acids may provide a means to improve it. OBJECTIVE: To investigate peri-operative erythrocyte function and effects of oral omega-3 fatty acids in morbidly obese women undergoing gastric bypass surgeryMETHODS:Fifty-six morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery were randomized between a low calorie diet (LCD) during 2 weeks or oral omega-3 poly-unsaturated fatty acids (n-3 PUFAs) and a normal diet during 4 weeks. Peri-operative blood samples were analyzed with the Lorrca MaxSIS Ektacytometer for erythrocyte deformability and aggregability. RESULTS: There were no significant differences in erythrocyte function between the groups at any time point. Only erythrocyte aggregability parameters were affected by surgery. At six month follow-up, aggregation index (AI) and cholesterol, glucose and insulin were significantly improved. CONCLUSIONS: In this study, oral Omega-3 supplementation did not affect erythrocyte function compared to a LCD. Six months after surgery a significant improvement in AI and metabolic parameters was observed in both groups, contributing to a reduction in the risk at thromboembolic and cardiovascular complications.


Assuntos
Suplementos Nutricionais/análise , Agregação Eritrocítica/efeitos dos fármacos , Deformação Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/efeitos dos fármacos , Ácidos Graxos Ômega-3/uso terapêutico , Derivação Gástrica/métodos , Laparoscopia/métodos , Obesidade Mórbida/cirurgia , Adolescente , Adulto , Idoso , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Intestinos/efeitos dos fármacos , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
6.
Acta Trop ; 207: 105466, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32302690

RESUMO

Omega-3 and omega-6 polyunsaturated fatty acids are synthesized from the essential fatty acids alpha-linolenic acid and linoleic acid, respectively. They are pivotal components of all mammalian cells and were found to be useful in prevention and treatment of a variety of health problems owing to their anti-inflammatory and anti-microbial properties. Omega-3 and omega-6 polyunsaturated fatty acids are further metabolized to anti-inflammatory mediators, such as lipoxins, resolvins, and protectins. Moreover, these polyunsaturated fatty acids were found to have in vivo and in vitro protective efficacies against some parasitic infections. Therefore, dietary intake of polyunsaturated fatty acids should be encouraged because of their considerable beneficial effects.


Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Doenças Parasitárias/prevenção & controle , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Ácidos Graxos Insaturados/classificação , Humanos
7.
Acta Diabetol ; 57(7): 853-860, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32114641

RESUMO

AIMS: Gut microbiota significantly impacts human health and is influenced by dietary changes. We evaluated the effects of diets naturally rich in polyphenols (PP) and/or long-chain n-3 polyunsaturated fatty acids (LCn3) on microbiota composition in an ancillary analysis of a randomized controlled trial in individuals at high cardiometabolic risk. METHODS: Seventy-eight individuals with high waist circumference and at least one additional component of the metabolic syndrome were randomized to an isoenergetic 8-week diet: (a) low LCn3 and PP; (b) high LCn3; (c) high PP; or (d) high LCn3 and PP. Microbiota analysis was performed on feces collected before and after the intervention. DGGE analysis of the predominant bacteria, Eubacterium rectale and Blautia coccoides group (Lachnospiraceae, EREC), Clostridium leptum (Ruminococcaceae, CLEPT), Bacteroides spp., Bifidobacteria, and Lactobacillus group was performed. A quantitative real-time PCR was performed for the same group, additionally including Atopobium cluster (Coriobatteriaceae). Before and after the intervention, participants underwent a 75 g OGTT and a high-fat test meal to evaluate glucose and lipid response. RESULTS: Adherence to the four diets was optimal. PP significantly increased microbial diversity (p = 0.006) and CLEPT (p = 0.015), while it reduced EREC (p = 0.044). LCn3 significantly increased the numbers of Bifidobacteria (p = 0.041). Changes in CLEPT numbers correlated with changes in early insulin secretion (r = 0.263, p = 0.030). Changes in Atopobium numbers correlated with postprandial triglycerides in plasma (r = 0.266, p = 0.026) and large VLDL (r = 0.313, p = 0.009), and cholesterol in large VLDL (r = 0.319, p = 0.008). CONCLUSIONS: Diets naturally rich in PP or LCn3 influenced gut microbiota composition in individuals at high cardiometabolic risk. These modifications were associated with changes in glucose/lipid metabolism.


Assuntos
Doenças Cardiovasculares/microbiologia , Dieta , Ácidos Graxos Ômega-3/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Síndrome Metabólica/microbiologia , Polifenóis/farmacologia , Adulto , Idoso , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Ácidos Graxos Ômega-3/administração & dosagem , Fezes/microbiologia , Feminino , Humanos , Masculino , Refeições , Síndrome Metabólica/dietoterapia , Síndrome Metabólica/etiologia , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Polifenóis/administração & dosagem , Fatores de Risco
8.
Diabetes Res Clin Pract ; 162: 108120, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32194222

RESUMO

BACKGROUND: Nrf2 is a transcription factor that induces the expression of several proteins with antioxidant properties such as sestrin2 (Sesn2) and is therefore considered as the major regulator of anti-oxidative defence system. OBJECTIVES: The aim of this research was to study the effect of supplementation with n-3 PUFAs on the antioxidant status and the gene expression of Nrf2 and Sestrin2 (Sesn2) in patients with type 2 diabetes mellitus (T2DM). PARTICIPANTS: Sixty patients with T2DM were enrolled in a placebo-controlled, double-blind, randomised clinical trial. INTERVENTION AND DESIGN: The participants were randomly allocated to two intervention groups receiving either n-3 PUFAs (2,700 mg/day) (n = 30) or placebo soft gels containing 900 mg of edible paraffin (n = 30). The main outcome measures were the expression of Sesn2 and Nrf2 genes which were assessed in peripheral blood mononuclear cells (PBMCs) after RNA extraction and cDNA synthesis by real-time PCR. Total antioxidant status in plasma samples was also measured based on the ferric reducing ability of plasma. RESULTS: NRF2 gene expression was significantly increased in n-3 PUFA-supplemented subjects, compared with the placebo group. Plasma total antioxidant status was also significantly augmented in n-3 PUFA-supplemented subjects. SESN2 gene expression was not significantly affected by n-3 PUFA supplementation although a slight up-regulation was observed. CONCLUSION: Supplementation with n-3 PUFAs enhanced NRF2 gene expression and improved overall antioxidant capacity and thus might be considered beneficial in the amelioration of oxidative stress and prevention of T2DM complications. TRIAL REGISTRATION: IRCT20150926024198N4.


Assuntos
Antioxidantes/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Expressão Gênica/genética , Fator 2 Relacionado a NF-E2/metabolismo , Idoso , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
PLoS One ; 15(3): e0230647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210469

RESUMO

The beneficial effects of omega (ω)-3 polyunsaturated fatty acid (PUFA) supplementation on major depressive disorder have been actively studied, but the underlying mechanism remains unknown. The present study examined the involvement of the nucleus accumbens (NAc) dopaminergic systems in behavioral changes in mice fed a diet high in ω-3 PUFAs. Mice fed a diet containing about double the amount of ω-3 PUFAs (krill oil (KO) diet) exerted shorter immobility times in the forced swim test (FST) than mice fed a control diet, containing only α-linolenic acid (ALA) as ω-3 PUFAs. The shorter immobility times were observed in both male and female mice. A dopamine metabolite, 3,4-dihydroxyphenylacetic acid, increased in the NAc in male mice fed the KO diet when compared with those fed the control diet. In addition, dopamine, 3-methoxytyramine, and homovanillic acid increased in the NAc in female mice fed the KO diet. Notably, the effects of the KO diet on the immobility time in the FST were abolished by microinjection of sulpiride, an antagonist of D2-like receptors, into the NAc. A similar microinjection of an antagonist selective for D1-like receptors, SKF83566, also abolished the reduction in immobility in the FST. Moreover, we found that tyrosine hydroxylase-positive cells increased in the ventral tegmental area (VTA) in mice fed the KO diet. These results suggest that modulation of the VTA-NAc dopaminergic pathway is one of the mechanisms by which a KO diet rich in ω-3 PUFAs reduces the immobility behavior in the mouse FST.


Assuntos
Antidepressivos/farmacologia , Dieta , Ácidos Graxos Ômega-3/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Animais , Antidepressivos/química , Comportamento Animal/efeitos dos fármacos , Monoaminas Biogênicas/análise , Monoaminas Biogênicas/metabolismo , Dopamina/metabolismo , Antagonistas de Dopamina/farmacologia , Ácidos Graxos Ômega-3/química , Feminino , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Núcleo Accumbens/metabolismo , Receptores de Dopamina D2/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/enzimologia
10.
Life Sci ; 245: 117393, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32017872

RESUMO

AIMS: Receptor for advanced glycation end products (RAGE) production is induced by diabetes. Microglial cells are activated by RAGE and produce inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and oxidative stress markers. Persistent production of TNF-α can provide a link between diabetes and Alzheimer's disease (AD). The purpose of this study was to investigate the effect of concomitant use of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) with iron supplements on microglial cell activation and inflammatory conditions in the hippocampus of type 2 diabetic rats. MAIN METHODS: Diabetic and normal Wistar rats were divided into six groups. Oxidative stress markers (total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA)), mRNA expression and protein levels of RAGE and TNF-α were evaluated in the hippocampus of the controls and supplemented with ferrous sulfate and ω-3 PUFAs alone and together rats. Also, the entry of microglia cells into the hippocampus was evaluated by immunohistochemistry technique. KEY FINDINGS: Levels of the microglial activation (2.4 fold, p < 0.0001), MDA (84%, p < 0.0001) and oxidative stress index (OSI) (11%, p = 0.0094), mRNA expression and protein contents of RAGE (1.83 fold and 82% respectively) and TNF-α (2.25 fold and 86% respectively) were strongly influenced by negative effect of iron compared to the group receiving only ω-3 PUFAs which was dramatically improved by vitamin E. SIGNIFICANCE: These observations indicated that the co-supplementation of ferrous sulfate with ω-3 PUFAs decreases the anti-inflammatory ability of ω-3 PUFAs in the hippocampus of diabetic rats via RAGE/TNF-α-induced oxidative stress pathway up-regulation.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Compostos Ferrosos/farmacologia , Hipocampo/efeitos dos fármacos , Animais , Hipocampo/química , Inflamação/tratamento farmacológico , Malondialdeído/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
Diabetes ; 69(4): 724-735, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32029482

RESUMO

Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H2O2) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H2O2 by high glucose, and H2O2 reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E-fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/farmacologia , Retinopatia Diabética/metabolismo , Ácido Eicosapentaenoico/farmacologia , Células Endoteliais/metabolismo , Células Ependimogliais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Neurônios Retinianos/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Eletrorretinografia , Células Endoteliais/efeitos dos fármacos , Células Ependimogliais/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Neurônios Retinianos/efeitos dos fármacos
12.
Oxid Med Cell Longev ; 2020: 4327470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32064024

RESUMO

Infections of the genital tract can perturb the fertility in humans and animals. Pathogen recognition and activation of innate immunity onset through the pattern recognition receptor activation, such as Toll-like receptor 4 (TLR4), leading to the production of proinflammatory cytokines and mediators. TLR4 is expressed both on leukocytes and nonimmune cells. Rabbit TLR4 shows great similarity to its human counterpart. Moreover, the TLR4 signalling pathway could be modulated by long-chain polyunsaturated fatty acids (LC-PUFA). The objectives of this study were (i) to determine the expression levels of TLR4 and proinflammatory cytokines in the reproductive hypothalamic-gonadal axis of the male rabbit and (ii) to evaluate if the n-3 PUFA-enriched diets can modify their expression levels in the tissues and LC-PUFA profiles in seminal plasma. Fifteen rabbit bucks (n = 5/experimental group) were fed with different diets: commercial standard (group C), rich in extruded linseed (10%, group L), and in fish oil (3%, group FO) for 110 days. TLR4, TNF-α, and IL-1ß mRNA were ubiquitously expressed throughout the hypothalamic-gonadal axis. However, TLR4 mRNA expression was lower in the hypothalamus than the epididymis (P < 0.01), seminal vesicles (P < 0.01), and pituitary gland (P < 0.05). Dietary enrichment in PUFA did not modify the gene expression profile nor the histological characteristics of the tissues. Conversely in seminal plasma, rabbits fed with L and FO had lower n-6 (P < 0.05), LC-PUFA n-6 (P < 0.05), and n-6/n-3 ratio (P < 0.05) but higher n-3 (P < 0.001) and LC-PUFA n-3 (P < 0.01) compared to the control group. Our study builds a map of the gene expression of TRL4 and proinflammatory cytokines in the reproductive hypothalamic-gonadal axis of the male rabbit, fundamental step for understanding the immune defence mechanisms. Diets enriched in LC-PUFA did not affect basal gene expression but modulated sperm fatty acid composition. Finally, rabbit may be an excellent animal model to study the relationship between inflammation and infertility, and the nutritional modulation of immune functions.


Assuntos
Ácidos Graxos Ômega-3/farmacologia , Hipotálamo/metabolismo , Interleucina-1beta/metabolismo , Testículo/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ração Animal , Animais , Dieta , Epididimo/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Óleos de Peixe/farmacologia , Inflamação/metabolismo , Óleo de Semente do Linho/farmacologia , Masculino , Hipófise/citologia , Hipófise/metabolismo , Hipófise/patologia , Coelhos , Glândulas Seminais/metabolismo , Espermatozoides/metabolismo , Testículo/citologia , Receptor 4 Toll-Like/genética
13.
Res Vet Sci ; 129: 137-153, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32000015

RESUMO

In dogs, decreasing telomere length is a biomarker for cellular aging. On a systemic level, aging affects the locomotor system in particular, leading to restricted joint mobility. As aging is thought to be related to oxidative stress, it may be counteracted by a diet enriched with antioxidants, mitochondrial cofactors and omega-3 fatty acids. This randomized, blinded and placebo-controlled study examined the influence of an accordingly enriched diet compared to a control diet on 36 young and 38 old shepherd dogs. At the outset, after 3 and after 6 months, mean and minimum telomere lengths were measured. Furthermore, minimum and maximum joint angles and range of motion of the shoulder, elbow, carpal, hip, stifle and tarsal joints were measured by computer-assisted gait analysis. A positive influence of the enriched diet on old dogs could be verified for minimum telomere length and all three parameters of the shoulder joint on the side with the higher vertical ground reaction force after 6 months. In the other joints there were less significant differences; in some cases they indicated a contrary influence of the enriched diet on young dogs, probably due to its reduced protein content. The greater effect of the enriched diet on minimum than on mean telomere length may be due to the higher preference of telomerase for short telomeres. The greater effect on shoulder joint mobility is explained by the greater influence of musculature and connective tissue in this joint. For elderly dogs it is advisable to feed these nutritional supplements.


Assuntos
Envelhecimento/fisiologia , Antioxidantes/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Mitocôndrias/metabolismo , Articulação do Ombro/fisiologia , Homeostase do Telômero/efeitos dos fármacos , Animais , Dieta/veterinária , Suplementos Nutricionais , Cães , Método Duplo-Cego , Estresse Oxidativo , Joelho de Quadrúpedes , Telômero/efeitos dos fármacos , Encurtamento do Telômero
14.
Lipids Health Dis ; 19(1): 4, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915015

RESUMO

BACKGROUND: Menopause predisposes individuals to affective disorders, such as depression, which is tightly related to neuroinflammation. While the neuroinflammatory condition has been demonstrated in ovariectomized (OVX) rodents, there is limited evidence concerning microglial polarization, a key process in brain immune activation, in menopause-related brain. METHODS: Therefore, the present study aims to evaluate the polarized microglia in long-term OVX rats and we further explored whether supplementation of ω-3 polyunsaturated fatty acids (PUFA), the pleiotropic bioactive nutrient, is effective in the neurobehavioral changes caused by OVX. RESULTS: Our data showed that OVX-induced anxiety and depression-like behaviors in rats, accompanied with increased neural apoptosis and microglial activation in the hippocampus. Additionally, OVX enhanced proinflammatory cytokines expression and suppressed the expression of anti-inflammatory cytokine, IL-10. Correspondingly, OVX reinforced NFκB signaling and shifted the microglia from immunoregulatory M2 phenotype to proinflammatory M1 phenotype. Meanwhile, daily supplementation with PUFA suppressed microglial M1 polarization and potentiated M2 polarization in OVX rats. In parallel, PUFA also exerted antidepressant and neuroprotective activities, accompanied with neuroimmune-modulating actions. CONCLUSION: Collectively, the present study firstly demonstrated the disturbed microglial polarization in the OVX brain and provide novel evidence showing the association between the antidepressant actions of PUFA and the restraint neuroinflammatory progression.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Ácidos Graxos Ômega-3/farmacologia , Interleucina-10/genética , Animais , Depressão/genética , Depressão/patologia , Modelos Animais de Doenças , Ácidos Graxos Insaturados/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/patologia , NF-kappa B/genética , Ratos , Transdução de Sinais/efeitos dos fármacos
15.
Int J Mol Sci ; 21(2)2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31947691

RESUMO

The arrhythmogenic potential of ß1-adrenoceptor autoantibodies (ß1-AA), as well as antiarrhythmic properties of omega-3 in heart diseases, have been reported while underlying mechanisms are poorly understood. We aimed to test our hypothesis that omega-3 (eicosapentaenoic acid-EPA, docosahexaenoic acid-DHA) may inhibit matrix metalloproteinase (MMP-2) activity to prevent cleavage of ß1-AR and formation of ß1-AA resulting in attenuation of pro-arrhythmic connexin-43 (Cx43) and protein kinase C (PKC) signaling in the diseased heart. We have demonstrated that the appearance and increase of ß1-AA in blood serum of male and female 12-month-old spontaneously hypertensive rats (SHR) was associated with an increase of inducible ventricular fibrillation (VF) comparing to normotensive controls. In contrast, supplementation of hypertensive rats with omega-3 for two months suppressed ß1-AA levels and reduced incidence of VF. Suppression of ß1-AA was accompanied by a decrease of elevated myocardial MMP-2 activity, preservation of cardiac cell membrane integrity and Cx43 topology. Moreover, omega-3 abrogated decline in expression of total Cx43 as well as its phosphorylated forms at serine 368 along with PKC-ε, while decreased pro-fibrotic PKC-δ levels in hypertensive rat heart regardless the sex. The implication of MMP-2 in the action of omega-3 was also demonstrated in cultured cardiomyocytes in which desensitization of ß1-AR due to permanent activation of ß1-AR with isoproterenol was prevented by MMP-2 inhibitor or EPA. Collectively, these data support the notion that omega-3 via suppression of ß1-AA mechanistically controlled by MMP-2 may attenuate abnormal of Cx43 and PKC-ε signaling; thus, abolish arrhythmia substrate and protect rats with an advanced stage of hypertension from malignant arrhythmias.


Assuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/etiologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Ácidos Graxos Ômega-3/farmacologia , Hipertensão/complicações , Receptores Adrenérgicos beta 1/imunologia , Animais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Biomarcadores , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Conexina 43/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Ácidos Graxos Ômega-3/metabolismo , Feminino , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/ultraestrutura , Proteína Quinase C-épsilon/metabolismo , Ratos , Ratos Endogâmicos SHR , Sarcolema/metabolismo , Sarcolema/ultraestrutura , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/fisiopatologia
16.
Eur J Histochem ; 64(1)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31988533

RESUMO

Emerging evidence suggests that red blood cells (RBCs) are involved in many functions essential for life. Nuclear factor-kB (NF-kB), nitric oxide synthases (inducible nitric oxide synthase -iNOS-, endothelial nitric oxide synthase -eNOS-) and interleukin-1ß (-IL-1ß-) are all proteins that have been identified in RBCs. In nucleated cells, such as white blood cells (WBCs), these proteins have well investigated roles, linked to stress and inflammation. It is not the same in erythrocytes, for this reason, we considered obese patients for studying the morphology of RBCs. We studied a possible correlation between their morphological changes and several protein expressions. Moreover, we compared the results about the aforementioned proteins and antioxidant markers with those obtained in WBCs from healthy and obese patients before and after omega-3 polyunsaturated fatty acid supplementation. This latter scientific point is important in order to determine whether there are differences in the expression of nucleated and anucleated cells. The morphology of RBCs changed in obese patients, but it is significantly restored after six weeks of supplementation. The expression of antioxidant enzymes changed in RBCs and WBCs in obesity but all proteins restore their positivity after supplementation. We found that: the presence of NF-kB, antioxidant enzymes and eNOS in healthy RBCs could indicate a role of these proteins as regulators of cellular metabolism; obese WBCs showed a higher NF-kB, iNOS and IL-1ß positivity, whereas eNOS presence did not significantly change in these cells. We tried to explain the different positivity of NF-kB, proposing a dual role for this protein, as prolifespan and as proinflammatory processes, depending on examined cells. In conclusion, we have considered the literature that focuses on the omega-6/omega-3 ratio. The ratio changed from the past, especially in people whose diet is strongly westernized worsening the state of health of the patient and leading to an higher incidence of obesity. Our study hypothesizes that the supplementation could help to restore the correct ratio.


Assuntos
Eritrócitos/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Obesidade/fisiopatologia , Adulto , Catalase/metabolismo , Eritrócitos/patologia , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Inflamação/fisiopatologia , Interleucina-1beta/metabolismo , Pessoa de Meia-Idade , Obesidade/patologia , Superóxido Dismutase-1/metabolismo
17.
Environ Toxicol ; 35(2): 231-241, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31639282

RESUMO

The present study examined the influence of co-exposure to cadmium (Cd) and nickel (Ni) on hepatorenal function as well as the protective role of omega-3 polyunsaturated fatty acids (ω-3FA) in rats. The animals were exposed to Cd (5 mg/kg) and Ni (150 µg/L in drinking water) singly or co-exposed to both metals and ω-3FA at 20 mg/kg for 14 consecutive days. Results showed that hepatorenal injury resulting from individual exposure to Cd or Ni was not aggravated in the co-exposure group. Moreover, ω-3FA markedly abrogated the reduction in the antioxidant enzyme activities, the increase in reactive oxygen and nitrogen species, and lipid peroxidation induced by Cd and Ni co-exposure. Additionally, ω-3FA administration markedly suppressed the increase in hepatic and renal myeloperoxidase activity, nitric oxide, tumor necrosis factor alpha, and interleukin-1 ß levels in the co-exposure group. Genotoxicity resulting from individual exposure to Cd or Ni was intensified in the co-exposure group. However, ω-3FA administration markedly ameliorated the genotoxicity and histological lesions in the co-exposure group. Taken together, co-exposure to Cd and Ni aggravated genotoxicity and not oxido-inflammatory stress in the liver and kidney of rats. ω-3FA abated hepatorenal injury and genotoxicity induced by Cd and Ni co-exposure in rats.


Assuntos
Cádmio/toxicidade , Ácidos Graxos Ômega-3/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Níquel/toxicidade , Animais , Biomarcadores/metabolismo , Sinergismo Farmacológico , Feminino , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
18.
Am J Clin Nutr ; 111(2): 385-395, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826232

RESUMO

BACKGROUND: The postoperative inflammatory response contributes to tissue healing and recovery but overwhelming inflammation is associated with postoperative complications. n-3 (ω-3) PUFAs modulate inflammatory responses and may help to prevent a proinflammatory cascade. OBJECTIVES: We aimed to investigate the effects of perioperative intravenous n-3 PUFAs on inflammatory cytokines in colon cancer surgery. METHODS: This study is a randomized, double-blind, placebo-controlled clinical trial. Forty-four patients undergoing elective colon resection for nonmetastasized cancer were randomly assigned to 2 intravenous n-3 PUFA or saline control infusions the night before and the morning after surgery. Blood was sampled at 6 perioperative time points for changes in cytokines in serum and in LPS-stimulated whole blood samples and leukocyte membrane fatty acid profiles. RESULTS: Twenty-three patients received saline and 21 patients received n-3 PUFAs. Patient and operation characteristics were equal between groups, except for open resection (saline n = 5 compared with n-3 PUFA n = 0, P = 0.056). Ex-vivo IL-6 after LPS stimulation was significantly higher in the n-3 PUFA group at the first day after surgery (P = 0.014), but not different at the second day after surgery (P = 0.467). White blood cell count was higher in the n-3 PUFA group at the fourth day after surgery (P = 0.029). There were more patients with infectious complications in the n-3 PUFA group (8 compared with 3, P = 0.036). There were no overall differences in serum IL-6, IL-10, C-reactive protein, and length of stay. The administration of n-3 PUFAs resulted in rapid increases in leukocyte membrane n-3 PUFA content. CONCLUSIONS: In the n-3 PUFA group a clear relation with serum and LPS-stimulated cytokines was not found but, unexpectedly, more infectious complications occurred. Caution is thus required with the off-label use of a perioperative intravenous n-3 PUFA emulsion as a standalone infusion in the time sequence reported in the present study in colon resections with primary anastomosis. This trial was registered at clinicaltrials.gov as NCT02231203.


Assuntos
Neoplasias do Colo/cirurgia , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Inflamação/prevenção & controle , Período Perioperatório , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Leucócitos/química , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade
19.
Biomed Pharmacother ; 121: 109631, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31715372

RESUMO

Although metformin (Met) is the most recommended anti-diabetogenic drug in type 2 diabetic state, the drug is known to compromise bone integrity. Like metformin, omega-3 fatty acids (ω-3) have gluco-regulatory action; however, it aids bone health. Therefore, the present study investigated the effects of ω-3 and/or metformin in diabetic rats. Fifty rats of ten animals per group were divided into the following: Control; Diabetic untreated; Diabetic + ω-3; Diabetic + metformin (metfm) and Diabetic + ω-3 + metf groups. Diabetes was induced by the administration of streptozotocin (65 mg/kg b.w., i.p.), 15 min after the administration of nicotinamide (110 mg/kg b.w., i.p.). Five days afterwards, treatments started and they lasted for 28 days. ω-3 and metformin were administered at 200 and 180 mg/kg b.w., p.o. respectively. The results showed that the induced diabetes was characterised by significant increases in calcium to phosphorus ratio, tartrate resistant acid phosphatase (TRAP), glucose and insulin resistance; but significant decreases in parathyroid hormone(PTH), phosphorus, TAC and hepatic glycogen. Relative to the diabetic control, treatments with ω-3 or metformin caused significant elevations in hepatic glycogen, total alkaline phosphatase (TALP), osteocalcin, PTH, estradiol, and calcium; however, significant decreases in TRAP and glucose. Co-administration of ω-3 and metformin caused more desirable effects on TALP, c-terminal telopeptide of type 1 collagen, estradiol and calcium to phosphorus ratio compared to the single administration. Relative to ω-3, melatonin showed a more favourable effect on calcium to phosphorus ratio; however, the former proved to have more desirable actions on insulin and TAC. Hence, it was concluded that the combined but not the single administration of ω-3 and metformin could be preferably used in the management of bone health in diabetic state.


Assuntos
Antioxidantes/metabolismo , Biomarcadores/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Ácidos Graxos Ômega-3/farmacologia , Metformina/farmacologia , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Cálcio/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Resistência à Insulina/fisiologia , Masculino , Ratos , Ratos Wistar , Estreptozocina/farmacologia
20.
Int J Mol Sci ; 20(24)2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31847143

RESUMO

Dietary supplementation with omega-3 and omega-6 fatty acids offer cardioprotection against air pollution, but these protections have not been established in the brain. We tested whether diets rich in omega-3 or -6 fatty acids offered neuroprotective benefits, by measuring mitochondrial complex enzyme I, II and IV activities and oxidative stress measures in the frontal cortex, cerebellum, hypothalamus, and hippocampus of male rats that were fed either a normal diet, or a diet enriched with fish oil olive oil, or coconut oil followed by exposure to either filtered air or ozone (0.8 ppm) for 4 h/day for 2 days. Results show that mitochondrial complex I enzyme activity was significantly decreased in the cerebellum, hypothalamus and hippocampus by diets. Complex II enzyme activity was significantly lower in frontal cortex and cerebellum of rats maintained on all test diets. Complex IV enzyme activity was significantly lower in the frontal cortex, hypothalamus and hippocampus of animals maintained on fish oil. Ozone exposure decreased complex I and II activity in the cerebellum of rats maintained on the normal diet, an effect blocked by diet treatments. While diet and ozone have no apparent influence on endogenous reactive oxygen species production, they do affect antioxidant levels in the brain. Fish oil was the only diet that ozone exposure did not alter. Microglial morphology and GFAP immunoreactivity were assessed across diet groups; results indicated that fish oil consistently decreased reactive microglia in the hypothalamus and hippocampus. These results indicate that acute ozone exposure alters mitochondrial bioenergetics in brain and co-treatment with omega-6 and omega-3 fatty acids alleviate some adverse effects within the brain.


Assuntos
Encéfalo/metabolismo , Óleo de Coco/farmacologia , Metabolismo Energético/efeitos dos fármacos , Óleos de Peixe/farmacologia , Mitocôndrias/metabolismo , Azeite de Oliva/farmacologia , Animais , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Microglia/metabolismo , Ratos , Ratos Endogâmicos WKY
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