RESUMO
Trans-resveratrol, a widely used supplement for humans, aims to enhance the body's antioxidant defense. Studies suggest that it exerts anti-inflammatory and antioxidant effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2). In order to evaluate this hypothesis, LDLr(-/-) mice were fed a Western diet to induce liver inflammation and oxidative stress. One group was fed a diet containing 0.60â mg/day of trans-resveratrol (RESV), while another group received no dietary supplementation (CONT). Oxidative stress biomarkers and inflammatory cytokines were assessed in liver homogenates. It was observed that trans-resveratrol decreased hepatic oxidative stress by increasing the GSH/GSSG ratio and reducing malondialdehyde (MDA) concentration. However, the RESV group exhibited a reduction in Nrf2 relative expression compared to CONT. Additionally, trans-resveratrol supplementation reduced nuclear factor-κB (NF-κB) expression but led to an increase in IL-6, with no significant changes observed in tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) concentrations. Overall, these findings indicate that the in vivo antioxidant impact induced by trans-resveratrol supplementation in hepatic tissue did not correlate with increase of inflammatory cytokines and Nrf2 relative expression. Further exploration of alternative mechanisms, such as direct radical scavenger activity, is warranted to elucidate the antioxidant effect.
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Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multiple targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia-reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 h of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cytokines, oxidative stress, gene expression of apoptosis-related genes, TNF-α and caspase-3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the caspase-3 protein and a reduction in the TNF-α protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes, and their combination represents a promising therapeutic proposal against liver IRI.
Assuntos
Traumatismo por Reperfusão , Fator de Necrose Tumoral alfa , Ratos , Animais , Masculino , Humanos , Ratos Wistar , Caspase 3/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fígado/metabolismo , Apoptose , Citocinas/metabolismo , Suplementos Nutricionais , Traumatismo por Reperfusão/metabolismoRESUMO
Nonalcoholic steatohepatitis (NASH) is considered growing risk factor for hepatocellular carcinoma development in high-income countries. Diet- and chemically induced rodent models have been applied for the translational study of NASH-associated hepatocarcinogenesis due to their morphological and molecular similarities to the corresponding human disease. Arctium lappa L. (burdock) root tea has been extensively consumed in Traditional Chinese Medicine due to its potential therapeutic properties. Indeed, the bioactive compounds of A. lappa root, as the polyphenols, have already showed antioxidant and anti-inflammatory properties in different in vivo and in vitro bioassays. In this study, we investigated whether burdock root ethanolic extract (BRE) administration attenuates NASH-associated hepatocarcinogenesis. Eight-week-old male Wistar rats received choline-deficient high-fat diet for 8 weeks and multiple thioacetamide doses for 4 weeks in order to induce NASH and preneoplastic glutathione-S-transferase pi (GST-P)+ preneoplastic foci. Subsequently, rats were treated with BRE (100 or 200 mg/kg body weight) or vehicle by oral gavage for 2 weeks. BRE displayed high levels of chlorogenic and caffeic acids and BRE administration reduced total fatty acid and lipid hydroperoxide levels, while increasing the activities of antioxidant superoxide dismutase and catalase enzymes in the liver. Furthermore, burdock intervention diminished the size of GST-P+ remodeling preneoplastic lesions (PNLs) and displayed a trend on reducing hepatocyte proliferation (Ki-67) inside them. These findings suggest that short-term exposure to BRE alleviated remodeling PNL development in NASH-associated hepatocarcinogenesis.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Arctium/química , Neoplasias Hepáticas/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Lesões Pré-Cancerosas/prevenção & controle , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Ácidos Cafeicos , Dieta Hiperlipídica/efeitos adversos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Medicina Tradicional Chinesa , Hepatopatia Gordurosa não Alcoólica/patologia , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Wistar , Tioacetamida/toxicidadeRESUMO
Atherosclerosis is the underlying cause of major cardiovascular events. The development of atherosclerotic plaques begins early in life, indicating that dietary interventions in childhood might be more effective at preventing cardiovascular disease (CVD) than treating established CVD in adulthood. Although plant sterols are considered safe and consistently effective in lowering plasma cholesterol, the health effects of early-life supplementation are unclear. Studies suggest there is an age-dependent effect on plant sterol metabolism: at a younger age, plant sterol absorption might be increased, while esterification and elimination might be decreased. Worryingly, the introduction of low-cholesterol diets in childhood may unintentionally favor a higher intake of plant sterols. Although CVD prevention should start as early as possible, more studies are needed to better elucidate the long-term effects of plant sterol accumulation and its implication on child development.
Assuntos
Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Fitosteróis/metabolismo , Suplementos Nutricionais , Humanos , Absorção Intestinal , Metabolismo dos Lipídeos/fisiologiaRESUMO
Echium oil is rich in omega-3, however, is unstable. The objective of this work was the co-encapsulation of echium oil and sinapic acid (SA) by emulsification using Arabic gum as emulsifier/carrier, followed by spray or freeze-drying. Eight treatments (S0, S200, S600 and S1000: particles spray dried with different concentrations of SA; L0, L200, L600 and L1000: particles freeze dried with different concentrations of SA) were analyzed in relation to microscopy, water activity (Aw), hygroscopicity, moisture, solubility, particle size, X-ray diffraction, thermogravimetry and accelerated oxidation. Particles of rounded shape and undefined form were obtained by spray and freeze-drying, besides ideal physicochemical properties for application (values from 0.091 to 0.365, 3.22 to 4.89%, 57 to 68% and 2.32 to 12.42 µm for Aw, moisture, solubility and particle size, respectively). All treatments protected the oil against oxidation, obtaining induction time of 5.31 h for oil and from 7.88 to 12.94 h for treatments. The better protection to oil was obtained with it emulsified and freeze-dried (L600); the encapsulation increased oxidative stability of the oil, besides facilitating its application over the fact the material is in powder form.
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Pannexins are transmembrane proteins that form communication channels connecting the cytosol of an individual cell with its extracellular environment. A number of studies have documented the presence of pannexin1 in liver as well as its involvement in inflammatory responses. In this study, it was investigated whether pannexin1 plays a role in acute liver failure and non-alcoholic steatohepatitis, being prototypical acute and chronic liver pathologies, respectively, both featured by liver damage, oxidative stress and inflammation. To this end, wild-type and pannexin1-/- mice were overdosed with acetaminophen for 1, 6, 24 or 48h or were fed a choline-deficient high-fat diet for 8weeks. Evaluation of the effects of genetic pannexin1 deletion was based on a number of clinically relevant read-outs, including markers of liver damage, histopathological analysis, lipid accumulation, protein adduct formation, oxidative stress and inflammation. In parallel, in order to elucidate molecular pathways affected by pannexin1 deletion as well as to mechanistically anchor the clinical observations, whole transcriptome analysis of liver tissue was performed. The results of this study show that pannexin1-/- diseased mice present less liver damage and oxidative stress, while inflammation was only decreased in pannexin1-/- mice in which non-alcoholic steatohepatitis was induced. A multitude of genes related to inflammation, oxidative stress and xenobiotic metabolism were differentially modulated in both liver disease models in wild-type and in pannexin1-/- mice. Overall, the results of this study suggest that pannexin1 may play a role in the pathogenesis of liver disease.
Assuntos
Conexinas/genética , Citoproteção/genética , Deleção de Genes , Hepatopatias/genética , Fígado/metabolismo , Proteínas do Tecido Nervoso/genética , Doença Aguda , Animais , Células Cultivadas , Doença Crônica , Modelos Animais de Doenças , Fígado/patologia , Hepatopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Fetal gastroschisis is a paraumbilical abdominal wall defect with herniation of abdominal organs. The underlying cause of the disease remains unknown; however, studies suggest that nutritional factors may play a role in its development. This prospective case-control study explored the association of serum fatty acid levels of pregnant women and occurrence of gastroschisis. Gastroschisis group comprised 57 pregnant women with fetuses with gastroschisis, and the control group comprised 114 pregnant women with normal fetuses. Serum fatty acids levels were compared between the groups for the overall pregnancy at <34 weeks; ≤25 weeks, and >25 and <34 weeks; and at delivery. Total fatty acids (p = .008), unsaturated fatty acids (p = .002), and the C18:1n9/C18:00 ratio (p = .021) were lower in the gastroschisis group than in the control group during the overall pregnancy; however, the C16:00/C18:2n6 ratio (p = .018) was higher in the gastroschisis group than in the control group during the same period. Total fatty acids (p = .044) and unsaturated fatty acids (p = .024) were lower in the gastroschisis group at ≤25 weeks, and unsaturated fatty acid (p = .025) and the C18:1n9/C18:00 ratio (p = .013) were lower in the gastroschisis group than in the control group at >25 and <34 weeks. Pregnant women with fetuses with gastroschisis have low serum fatty acids levels during pregnancy. These findings suggest that fatty acids levels may be involved in the pathogenesis of fetal gastroschisis.
Assuntos
Ácidos Graxos/sangue , Gastrosquise/sangue , Gastrosquise/mortalidade , Adolescente , Adulto , Biomarcadores , Estudos de Casos e Controles , Feminino , Gastrosquise/epidemiologia , Idade Gestacional , Humanos , Lipídeos/sangue , Metaboloma , Metabolômica/métodos , Gravidez , Adulto JovemRESUMO
Different pharmacological interventions have been applied with success to reduce the progression of atherosclerosis. However, many patients are not good responders or must interrupt treatment due to adverse effects. Bioactive compounds such as omega-3 fatty acids (n-3 FA), plant sterol esters (PSE) and phenolic compounds (PHC) are natural molecules with great potential to reduce the atherosclerosis burden by reducing inflammation, LDL cholesterol (LDL-C) and oxidative stress, respectively. Although their physiological effects on biomarkers are much lower than those expected by drugs used for the same purpose, bioactive compounds can easily be incorporated into the daily diet and present no adverse effects. However, little is known about the combination of n-3 FA, PSE, PHC, and drugs in atherosclerosis progression. This review article summarizes potential effects of co-therapies involving n-3 FA, PSE, and PHC combined with major hypolipidemic drugs on atherosclerosis biomarkers and clinical outcomes. Evidence of additive and/or complementary effects regarding drugs action reveals possible roles for bioactive compounds in disease management. Pharmaceutical companies, physicians, and food scientists should be prepared to better understand this type of interaction and its consequences in terms of efficacy and life quality.
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Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Ácidos Graxos Ômega-3/farmacologia , Hipolipemiantes/farmacologia , Fitosteróis/farmacologia , Polifenóis/farmacologia , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Linhagem Celular Tumoral , Colesterol/sangue , Dieta , Modelos Animais de Doenças , Humanos , Fatores de Risco , Triglicerídeos/sangueRESUMO
Liver fibrosis is the final common pathway for almost all causes of chronic liver injury. This chronic disease is characterized by excessive deposition of extracellular matrix components mainly due to transdifferentiation of quiescent hepatic stellate cell into myofibroblasts-like cells, which in turn is driven by cell death and inflammation. In the last few years, paracrine signaling through pannexin1 channels has emerged as a key player in the latter processes. The current study was set up to investigate the role of pannexin1 signaling in liver fibrosis. Wild-type and whole body pannexin1 knock-out mice were treated with carbon tetrachloride or subjected to bile duct ligation. Evaluation of the effects of pannexin1 deletion was based on a number of clinically relevant read-outs, including markers of liver damage, histopathological analysis, oxidative stress, inflammation and regenerative capacity. In parallel, to elucidate the molecular pathways affected by pannexin1 deletion as well as to mechanistically anchor the clinical observations, whole transcriptome analysis of liver tissue was performed. While pannexin1 knock-out mice treated with carbon tetrachloride displayed reduced collagen content, hepatic stellate cell activation, inflammation and hepatic regeneration, bile duct ligated counterparts showed increased hepatocellular injury and antioxidant enzyme activity with a predominant immune response. Gene expression profiling revealed a downregulation of fibrotic and immune responses in pannexin1 knock-out mice treated with carbon tetrachloride, whereas bile duct ligated pannexin1-deficient animals showed a pronounced inflammatory profile. This study shows for the first time an etiology-dependent role for pannexin1 signaling in experimental liver fibrosis.
Assuntos
Conexinas/genética , Cirrose Hepática/etiologia , Proteínas do Tecido Nervoso/genética , Animais , Ductos Biliares/cirurgia , Tetracloreto de Carbono/toxicidade , Conexinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Ligadura , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo/genética , Transdução de Sinais/genéticaRESUMO
Although a plethora of signaling pathways are known to drive the activation of hepatic stellate cells in liver fibrosis, the involvement of connexin-based communication in this process remains elusive. Connexin43 expression is enhanced in activated hepatic stellate cells and constitutes the molecular building stone of hemichannels and gap junctions. While gap junctions support intercellular communication, and hence the maintenance of liver homeostasis, hemichannels provide a circuit for extracellular communication and are typically opened by pathological stimuli, such as oxidative stress and inflammation. The present study was set up to investigate the effects of inhibition of connexin43-based hemichannels and gap junctions on liver fibrosis in mice. Liver fibrosis was induced by administration of thioacetamide to Balb/c mice for eight weeks. Thereafter, mice were treated for two weeks with TAT-Gap19, a specific connexin43 hemichannel inhibitor, or carbenoxolone, a general hemichannel and gap junction inhibitor. Subsequently, histopathological analysis was performed and markers of hepatic damage and functionality, oxidative stress, hepatic stellate cell activation and inflammation were evaluated. Connexin43 hemichannel specificity of TAT-Gap19 was confirmed in vitro by fluorescence recovery after photobleaching analysis and the measurement of extracellular release of adenosine-5'-triphosphate. Upon administration to animals, both TAT-Gap19 and carbenoxolone lowered the degree of liver fibrosis accompanied by superoxide dismutase overactivation and reduced production of inflammatory proteins, respectively. These results support a role of connexin-based signaling in the resolution of liver fibrosis, and simultaneously demonstrate the therapeutic potential of TAT-Gap19 and carbenoxolone in the treatment of this type of chronic liver disease.
Assuntos
Carbenoxolona/uso terapêutico , Conexina 43/antagonistas & inibidores , Cirrose Hepática/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carbenoxolona/administração & dosagem , Carbenoxolona/farmacologia , Células Cultivadas , Conexina 43/administração & dosagem , Conexina 43/farmacologia , Conexina 43/uso terapêutico , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/etiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Superóxido Dismutase/metabolismo , Tioacetamida/toxicidadeRESUMO
BACKGROUND: Omega-3 fatty acids (n3 FA) promote beneficial effects on cardiovascular diseases, but they are highly susceptible to oxidation, which leads to the formation of potentially toxic secondary products. In this study, the antioxidant capacity of natural compounds (sinapic acid and rutin) was evaluated using an accelerated model to oxidize the oils. Five inducers (temperature, Fe2+ , 2,2'-azobis(2-amidinopropane) dihydrochloride, ascorbyl palmitate and the hydrophobic 2,2'-azobis-2,4-dimethylvaleronitrile (AMVN)) were combined in a factorial design to accelerate the oxidation of three oils (flaxseed, echium and fish) containing different sources of n3 FA. RESULTS: Lipid hydroperoxide (LOOH) and thiobarbituric acid reactive substance (TBARS) concentrations estimated using the regression models did not differ from the observed values. AMVN + Fe2+ increased TBARS in all samples. CONCLUSION: The values for the oxidative markers obtained 48 h after induction were similar to those obtained when the oils were heated at 60 ° C for 15 days. Of a number of volatile compounds formed from the oxidation of different n3 FA sources, (E,E)-2,4-heptadienal, (E,E)-2,4-decadienal, decanal, undecanal and (E)-2-undecenal were identified in all samples and could be used as more specific oxidative markers. Using the accelerated model, rutin improved the oxidative stability of fish oil, probably due to the presence of a catechol group in its chemical structure. © 2017 Society of Chemical Industry.
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Ácidos Graxos Ômega-3/química , Óleos de Peixe/química , Óleos de Plantas/química , Echium/química , Linho/química , OxirreduçãoRESUMO
The aim of the present study was to investigate the relationship of four TNF-α SNP with inflammatory biomarkers and plasma fatty acids (FA), and the interaction among them in a population-based, cross-sectional study in São Paulo, Brazil. A total of 281 subjects, aged >19 and <60 years, participated in a cross-sectional, population-based study performed in Brazil. The following SNP spanning the TNF-α gene were genotyped: -238G/A (rs361525), -308G/A (rs1800629), -857C/T (rs1799724) and -1031T/C (rs1799964). In all, eleven plasma inflammatory biomarkers and plasma FA profile were determined. To analyse the interaction between TNF-α SNP and plasma FA, a cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups used as outcome: inflammatory (INF) and non-inflammatory clusters. The -238A allele carriers had higher TNF-α (P=0·033), IL-6 (P=0·013), IL-1ß (P=0·037), IL-12 (0·048) and IL-10 (P=0·010) than the GG genotype. The -308A allele carriers also had lower levels of plasma palmitoleic acid (P=0·009), oleic acid (P=0·039), total MUFA (P=0·014), stearoyl-CoA desaturase (SCD) activity index-16 (P=0·007), SCD-18 (P=0·020) and higher levels of PUFA (P=0·046) and DHA (P=0·044). Significant interactions modifying the risk of belonging to the INF cluster were observed with inflammatory cluster as outcome between -857C/T and plasma α-linolenic acid (P=0·026), and also between -308G/A and plasma stearic acid (P=0·044) and total SFA (P=0·040). Our study contributes to knowledge on TNF-α SNP and their association with inflammatory biomarker levels, plasma FA and the interaction among them, of particular interest for the Brazilian population.
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Ácidos Graxos/sangue , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Alelos , Biomarcadores/sangue , Brasil , Criança , Colesterol/sangue , Estudos Transversais , Exercício Físico , Ácidos Graxos Monoinsaturados/sangue , Feminino , Técnicas de Genotipagem , Humanos , Interleucinas/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Ácido Oleico/sangue , Ácidos Esteáricos/sangue , Estearoil-CoA Dessaturase/sangue , Estearoil-CoA Dessaturase/genética , Inquéritos e Questionários , Triglicerídeos/sangue , Circunferência da Cintura , Adulto Jovem , Ácido alfa-Linolênico/sangueRESUMO
Non-alcoholic steatohepatitis is a highly prevalent liver pathology featured by hepatocellular fat deposition and inflammation. Connexin32, which is the major building block of hepatocellular gap junctions, has a protective role in hepatocarcinogenesis and is downregulated in chronic liver diseases. However, the role of connexin32 in non-alcoholic steatohepatitis remains unclear. Connexin32-/- mice and their wild-type littermates were fed a choline-deficient high-fat diet. The manifestation of non-alcoholic steatohepatitis was evaluated based on a battery of clinically relevant read-outs, including histopathological examination, diverse indicators of inflammation and liver damage, in-depth lipid analysis, assessment of oxidative stress, insulin and glucose tolerance, liver regeneration and lipid-related biomarkers. Overall, more pronounced liver damage, inflammation and oxidative stress were observed in connexin32-/- mice compared to wild-type animals. No differences were found in insulin and glucose tolerance measurements and liver regeneration. However, two lipid-related genes, srebf1 and fabp3, were upregulated in Cx32-/- mice in comparison with wild-type animals. These findings suggest that connexin32-based signalling is not directly involved in steatosis as such, but rather in the sequelae of this process, which underlie progression of non-alcoholic steatohepatitis.
Assuntos
Conexinas/deficiência , Citocinas/metabolismo , Fígado , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Animais , Conexinas/genética , Citocinas/sangue , Proteína 3 Ligante de Ácido Graxo , Proteínas de Ligação a Ácido Graxo/genética , Junções Comunicantes/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Fígado/imunologia , Fígado/metabolismo , Fígado/ultraestrutura , Regeneração Hepática , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Regulação para Cima , Proteína beta-1 de Junções ComunicantesRESUMO
BACKGROUND: Although males contribute half of the embryo's genome, only recently has interest begun to be directed toward the potential impact of paternal experiences on the health of offspring. While there is evidence that paternal malnutrition may increase offspring susceptibility to metabolic diseases, the influence of paternal factors on a daughter's breast cancer risk has been examined in few studies. METHODS: Male Sprague-Dawley rats were fed, before and during puberty, either a lard-based (high in saturated fats) or a corn oil-based (high in n-6 polyunsaturated fats) high-fat diet (60 % of fat-derived energy). Control animals were fed an AIN-93G control diet (16 % of fat-derived energy). Their 50-day-old female offspring fed only a commercial diet were subjected to the classical model of mammary carcinogenesis based on 7,12-dimethylbenz[a]anthracene initiation, and mammary tumor development was evaluated. Sperm cells and mammary gland tissue were subjected to cellular and molecular analysis. RESULTS: Compared with female offspring of control diet-fed male rats, offspring of lard-fed male rats did not differ in tumor latency, growth, or multiplicity. However, female offspring of lard-fed male rats had increased elongation of the mammary epithelial tree, number of terminal end buds, and tumor incidence compared with both female offspring of control diet-fed and corn oil-fed male rats. Compared with female offspring of control diet-fed male rats, female offspring of corn oil-fed male rats showed decreased tumor growth but no difference regarding tumor incidence, latency, or multiplicity. Additionally, female offspring of corn oil-fed male rats had longer tumor latency as well as decreased tumor growth and multiplicity compared with female offspring of lard-fed male rats. Paternal consumption of animal- or plant-based high-fat diets elicited opposing effects, with lard rich in saturated fatty acids increasing breast cancer risk in offspring and corn oil rich in n-6 polyunsaturated fatty acids decreasing it. These effects could be linked to alterations in microRNA expression in fathers' sperm and their daughters' mammary glands, and to modifications in breast cancer-related protein expression in this tissue. CONCLUSIONS: Our findings highlight the importance of paternal nutrition in affecting future generations' risk of developing breast cancer.
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Neoplasias da Mama/etiologia , Exposição Paterna , Efeitos Tardios da Exposição Pré-Natal , Animais , Apoptose , Neoplasias da Mama/patologia , Proliferação de Células , Transformação Celular Neoplásica , Análise por Conglomerados , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Humanos , Lipídeos/química , Masculino , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Animais , Neoplasias Mamárias Experimentais , Carne , MicroRNAs , Plantas/química , Gravidez , Proteômica/métodos , Ratos , Espermatozoides/metabolismoRESUMO
Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies.
Assuntos
Neoplasias Mamárias Experimentais/etiologia , Selênio/administração & dosagem , Selênio/deficiência , 9,10-Dimetil-1,2-benzantraceno , Animais , Carcinogênese , Suplementos Nutricionais , Feminino , Masculino , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Liver fibrosis results from the perpetuation of the normal wound healing response to several types of injury. Despite the wealth of knowledge regarding the involvement of intracellular and extracellular signaling pathways in liver fibrogenesis, information about the role of intercellular communication mediated by gap junctions is scarce. METHODS: In this study, liver fibrosis was chemically induced by carbon tetrachloride in mice lacking connexin32, the major liver gap junction constituent. The manifestation of liver fibrosis was evaluated based on a series of read-outs, including collagen morphometric and mRNA analysis, oxidative stress, apoptotic, proliferative and inflammatory markers. RESULTS: More pronounced liver damage and enhanced collagen deposition were observed in connexin32 knockout mice compared to wild-type animals in experimentally triggered induced liver fibrosis. No differences between both groups were noticed in apoptotic signaling nor in inflammation markers. However, connexin32 deficient mice displayed decreased catalase activity and increased malondialdehyde levels. CONCLUSION: These findings could suggest that connexin32-based signaling mediates tissue resistance against liver damage by the modulation of the antioxidant capacity. In turn, this could point to a role for connexin32 signaling as a therapeutic target in the treatment of liver fibrosis.
Assuntos
Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Conexinas/deficiência , Cirrose Hepática Experimental/metabolismo , Fígado/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colágeno/metabolismo , Conexinas/genética , Citocinas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/etiologia , Cirrose Hepática Experimental/patologia , Testes de Função Hepática , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Proteína beta-1 de Junções ComunicantesRESUMO
To investigate the effect of Yerba Mate (YM) aqueous extract intake on the NF-kB pathway and AKT expression in the liver, muscle, and adipose tissue of rats submitted to a high-fat diet (HFD). Male Wistar rats were fed a control (CON) (n = 24) or a HFD (n = 24) for 12 weeks. Afterwards, rats received YM daily (1 g/kg body weight) for 4 weeks. Intake of YM aqueous extract reduced body weight gain (p < 0.05) and total blood cholesterol (p < 0.05) in the HFD group in comparison to the non-treated HFD group. HFD group demonstrated an increased glycemic response at 5 and 10 min after insulin injection. YM decreased the ratio between phosphorylated and total kinase inhibitor of κB (IKK), increased the ratio of phosphorylated to total form of protein kinase B (AKT) and reduced NF-κB phosphorylation in the liver of the HFD group. Our data suggest a beneficial role of YM in improving metabolic dysfunctions induced by HFD.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Ilex paraguariensis , Resistência à Insulina , Fígado/efeitos dos fármacos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Colesterol/sangue , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/prevenção & controle , Insulina/metabolismo , Insulina/farmacologia , Fígado/metabolismo , Masculino , Músculos/metabolismo , Obesidade/complicações , Fosforilação , Fitoterapia , Extratos Vegetais/uso terapêutico , Ratos Wistar , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND: This study evaluated the effect of inulin and okara flour on textural and sensory properties of probiotic soy yoghurt (SY) throughout 28 days of storage at 4 °C. Employing a 2(2) design, four formulations of SY produced from soymilk and fermented with an ABT-4 culture (Lactobacillus acidophilus La-5, Bifidobacterium animalis Bb-12 and Streptococcus thermophilus) were studied: SY-C (control); SY-I (with inulin); SY-O (with okara); SY-IO (with inulin + okara). RESULTS: The addition of okara and the refrigerated storage led to significant differences in the instrumental texture parameters of SY (P < 0.05). Inulin and okara did not affect SY sensory acceptability (P > 0.05), but there was a tendency for higher scores in the presence of inulin. On the other hand, the storage period, particularly at 21 days, was unfavourable regarding the acceptance of the different SY. CONCLUSION: The results showed that the addition of okara flour and the storage were significant factors to increase firmness of the soy yoghurts. SY acceptability was not affected by the incorporation of inulin or okara. These results suggest that okara, discarded as industrial waste, may be used in probiotic soy yoghurt, helping to increase the nutritional and functional properties without altering its acceptability.
Assuntos
Glycine max , Inulina/administração & dosagem , Proteínas de Plantas/administração & dosagem , Polissacarídeos/administração & dosagem , Probióticos/administração & dosagem , Sensação , Alimentos de Soja/análise , Bifidobacterium/metabolismo , Comportamento do Consumidor , Fermentação , Humanos , Resíduos Industriais , Lactobacillus acidophilus/metabolismo , Valor Nutritivo , Alimentos de Soja/microbiologia , Glycine max/químicaRESUMO
Fatty acids are precursors of inflammatory oxylipins. In the context of COVID-19, an excessive production of pro-inflammatory cytokines is associated with disease severity. The objective was to investigate whether the baseline omega 3/omega 6 fatty acids ratio and the oxylipins were associated with inflammation and oxidative stress in unvaccinated patients with COVID-19, classified according to the severity of the disease during hospitalization. This Prospective population-based cohort study included 180 hospitalized patients with COVID-19. The patients were classified into five groups according to the severity of their disease. Group 1 was the least severe and Group 5 was the most severe. Three specific types of fatty acids-eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA)-as well as their enzymatic and non-enzymatic oxylipins were determined using chromatography coupled mass spectrometry. There was no difference in the ratio of omega-3 to omega-6 fatty acids between the groups (p = 0.276). However, the EPA/AA ratio was lower in Group 4 compared to Group 1 (p = 0.015). This finding was associated with an increase in both C-Reactive Protein (p < 0.001) and Interleukin-6 (p = 0.002). Furthermore, the concentration of F2-Isoprostanes was higher in Group 4 than in Group 1 (p = 0.009), while no significant changes were observed for other oxylipins among groups. Multivariate analysis did not present any standard of biomarkers, suggesting the high complexity of factors involved in the disease severity. Our hypothesis was confirmed in terms of EPA/AA ratio. A higher EPA/AA ratio upon hospital admission was found to be associated with lower concentration of C-Reactive Protein and Interleukin-6, leading to a better prognosis of hospitalized SARS-CoV-2 patients. Importantly, this beneficial outcome was achieved without any form of supplementation. The trial also provides important information that can be further applied to reduce the severity of infections associated with an uncontrolled synthesis of pro-inflammatory cytokines.Trial registration: https://clinicaltrials.gov/study/NCT04449718 -01/06/2020. ClinicalTrials.gov Identifier: NCT04449718.
Assuntos
COVID-19 , Ácidos Graxos Ômega-3 , Hospitalização , Índice de Gravidade de Doença , Humanos , COVID-19/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Ácidos Graxos Ômega-3/sangue , Idoso , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Oxilipinas/sangue , Ácido Eicosapentaenoico/sangue , Estresse Oxidativo , Ácidos Docosa-Hexaenoicos/sangue , Adulto , Inflamação/sangueRESUMO
BACKGROUND: In an effort to identify new alternatives for long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) supplementation, the effect of three sources of omega 3 fatty acids (algae, fish and Echium oils) on lipid profile and inflammation biomarkers was evaluated in LDL receptor knockout mice. METHODS: The animals received a high fat diet and were supplemented by gavage with an emulsion containing water (CON), docosahexaenoic acid (DHA, 42.89%) from algae oil (ALG), eicosapentaenoic acid (EPA, 19.97%) plus DHA (11.51%) from fish oil (FIS), and alpha-linolenic acid (ALA, 26.75%) plus stearidonic acid (SDA, 11.13%) from Echium oil (ECH) for 4 weeks. RESULTS: Animals supplemented with Echium oil presented lower cholesterol total and triacylglycerol concentrations than control group (CON) and lower VLDL than all of the other groups, constituting the best lipoprotein profile observed in our study. Moreover, the Echium oil attenuated the hepatic steatosis caused by the high fat diet. However, in contrast to the marine oils, Echium oil did not affect the levels of transcription factors involved in lipid metabolism, such as Peroxisome Proliferator Activated Receptor α (PPAR α) and Liver X Receptor α (LXR α), suggesting that it exerts its beneficial effects by a mechanism other than those observed to EPA and DHA. Echium oil also reduced N-6/N-3 FA ratio in hepatic tissue, which can have been responsible for the attenuation of steatosis hepatic observed in ECH group. None of the supplemented oils reduced the inflammation biomarkers. CONCLUSION: Our results suggest that Echium oil represents an alternative as natural ingredient to be applied in functional foods to reduce cardiovascular disease risk factors.