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Blood selenium (Se) concentrations differ substantially by population and could be influenced by genetic variants, increasing Se deficiency-related diseases. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with serum Se deficiency in 382 adults with admixed ancestry. Genotyping arrays were combined to yield 90,937 SNPs. R packages were applied to quality control and imputation. We also performed the ancestral proportion analysis. The Search Tool for the Retrieval of Interacting Genes was used to interrogate known protein-protein interaction networks (PPIs). Our ancestral proportion analysis estimated 71% of the genome was from Caucasians, 22% was from Africans, and 8% was from East Asians. We identified the SNP rs1561573 in the TraB domain containing 2B (TRABD2B), rs425664 in MAF bZIP transcription factor (MAF), rs10444656 in spermatogenesis-associated 13 (SPATA13), and rs6592284 in heat shock protein nuclear import factor (HIKESHI) genes. The PPI analysis showed functional associations of Se deficiency, thyroid hormone metabolism, NRF2-ARE and the Wnt pathway, and heat stress. Our findings show evidence of a genetic association between Se deficiency and metabolic pathways indirectly linked to Se regulation, reinforcing the complex relationship between Se intake and the endogenous factors affecting the Se requirements for optimal health.
Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Selênio , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Brasil , Predisposição Genética para Doença , Genótipo , Mapas de Interação de Proteínas/genética , Selênio/sangue , Selênio/deficiência , População Branca/genética , População Africana , População do Leste AsiáticoRESUMO
The objective was to assess aspartame excretion in saliva and the salivary insulin, total protein (TP), and alpha-amylase (AMI) levels in response to the ingestion of sweetened beverages (sodium cyclamate, aspartame, acesulfame, and sucrose). Fifteen healthy participants were included in a single-blinded trial with the intake of Diet soft drink, Regular soft drink, Water + sweeteners, Low sucrose content (3.5 g), and Water (blank) in 5 different days. In each day, saliva was collected at T0 (fasting), T1 (15 min after test-drink intake), T2 (30 min), T3 (60 min), and T4 (120 min) for the measurement of salivary aspartame (HPLC), TP, AMI (ELISA assays) and insulin levels (chemiluminescence). Chi-square, Friedman, ANOVA and Spearman correlation tests were applied. The late-perceived sweet/sour residual flavor was reported at a frequency of 80%, 60% and 20% after ingestion of artificially sweetened drinks, beverages with sucrose, and plain water, respectively (p < 0.05). Aspartame was detected in saliva after artificially sweetened drinks intake, with highest area under the peak for the Diet soft drink (p = 0.014). No change was observed for TP and AMI levels during the 120 min. Insulin levels increased 1 h after soft-drinks ingestion (regular and diet), while the levels did not change for Low sucrose content and Water + sweeteners test-drinks. Salivary aspartame correlated with insulin levels only after Diet soft drink intake (rho ≥ 0.7; p < 0.05). As aspartame can be detected in saliva and swallowed again until completely excreted, these results contribute to the knowledge of the biological fate of artificial sweeteners and the study of health outcomes.
Assuntos
Aspartame , Bebidas Adoçadas com Açúcar , Humanos , Edulcorantes , Insulina , Método Simples-Cego , alfa-Amilases , Sacarose , ÁguaRESUMO
The cururu toad (Rhinella jimi) is an anuran belonging to the fauna of the Brazilian northeast region, which releases a secretion with toxins from your parotoid glands. Although it has some information about secondary metabolites and proteins, the elemental composition of the released secretion is unknown. Therefore, this is the first report on the ionome of the secretion of the parotoid glands from R. jimi, investigating the influences of abiotic factors such as biome, seasonality, and gender. ICP-MS was used for measurements combined with principal component analysis (PCA). A screening of the secretion sample detected 68 elements which the total concentration of 18 elements was determined. PCA revealed that biome and seasonality factors have a greater influence on the ionomic profile of parotoid secretion. The presence of toxic metals in the secretion samples indicates that the R. jimi toad can be considered a potential bioindicator. These findings may contribute to understanding the metabolism, lifestyle, and interaction of the R. jimi toad with environmental factors as well as open new perspectives to investigate the relationships of the ionome with other biomolecules, for example, metalloproteins and their physiological functions.
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Venenos de Anfíbios , Bufonidae , Animais , Venenos de Anfíbios/metabolismo , Brasil , Bufonidae/metabolismo , Glândula Parótida/metabolismoRESUMO
Although the molecular mechanisms underlying methylmercury toxicity are not entirely understood, the observed neurotoxicity in early-life is attributed to the covalent binding of methylmercury to sulfhydryl (thiol) groups of proteins and other molecules being able to affect protein post-translational modifications from numerous molecular pathways, such as glutamate signaling, heat-shock chaperones and the antioxidant glutaredoxin/glutathione system. However, for other organomercurials such as ethylmercury or thimerosal, there is not much information available. Therefore, this review critically discusses current knowledge about organomercurials neurotoxicity-both methylmercury and ethylmercury-following intrauterine and childhood exposure, as well as the prospects and future needs for research in this area. Contrasting with the amount of epidemiological evidence available for methylmercury, there are only a few in vivo studies reporting neurotoxic outcomes and mechanisms of toxicity for ethylmercury or thimerosal. There is also a lack of studies on mechanistic approaches to better investigate the pathways involved in the potential neurotoxicity caused by both organomercurials. More impactful follow-up studies, especially following intrauterine and childhood exposure to ethylmercury, are necessary. Childhood vaccination is critically important for controlling infectious diseases; however, the safety of mercury-containing thimerosal and, notably, its effectiveness as preservative in vaccines are still under debate regarding its potential dose-response effects to the central nervous system.
Assuntos
Mercúrio , Compostos de Metilmercúrio , Síndromes Neurotóxicas , Vacinas , Humanos , Timerosal/toxicidade , Compostos de Metilmercúrio/toxicidade , Conservantes Farmacêuticos , Síndromes Neurotóxicas/etiologia , Compostos de SulfidrilaRESUMO
The presence of phthalates constitutes a risk to the health of aquatic environments and organisms. This work aimed to evaluate the toxic effects of di-iso-pentyl-phthalate (DiPeP) at environmentally relevant concentrations of 5, 25, and 125 µg/L in Danio rerio after subchronic exposure for 14 days. DiPeP altered the antioxidant system in the liver (125 µg/L), intestine (25 µg/L), brain, and gills in all concentrations tested. In animals exposed to 125 µg/L, DNA damage was identified in the gills. In addition, loss of cell boundary of hepatocytes, vascular congestion, necrosis in the liver, and presence of immune cells in the intestinal lumen were observed. Erythrocytic nuclear alterations in the blood occurred in animals exposed to 25 µg/L. DiPeP was quantified in muscle tissue at all exposure concentrations, appearing in a concentration-dependent manner. Contaminants such as DiPeP will still be used for a long time, mainly by industries, being a challenge for industry versus environmental health.
Assuntos
Ácidos Ftálicos , Poluentes Químicos da Água , Animais , Peixe-Zebra/fisiologia , Ácidos Ftálicos/toxicidade , Fígado , Modelos Teóricos , Poluentes Químicos da Água/toxicidadeRESUMO
Background: Pre-diabetes precedes Diabetes Mellitus (DM) disease and is a critical period for hyperglycemia treatment, especially for menopausal women, considering all metabolic alterations due to hormonal changes. Recently, the literature has demonstrated the role of physical exercise in epigenetic reprogramming to modulate the gene expression patterns of metabolic conditions, such as hyperglycemia, and prevent DM development. In the present study, we hypothesized that physical exercise training could modify the epigenetic patterns of women with poor glycemic control. Methods: 48 post-menopause women aged 60.3 ± 4.5 years were divided according to their fasting blood glucose levels into two groups: Prediabetes Group, PG (n=24), and Normal Glucose Group, NGG (n=24). All participants performed 14 weeks of physical exercise three times a week. The Infinium Methylation EPIC BeadChip measured the participants' Different Methylated Regions (DMRs). Results: Before the intervention, the PG group had 12 DMRs compared to NGG. After the intervention, five DMRs remained different. Interestingly, when comparing the PG group before and after training, 118 DMRs were found. The enrichment analysis revealed that the genes were related to different biological functions such as energy metabolism, cell differentiation, and tumor suppression. Conclusion: Physical exercise is a relevant alternative in treating hyperglycemia and preventing DM in post-menopause women with poor glycemic control.
Assuntos
Diabetes Mellitus , Hiperglicemia , Estado Pré-Diabético , Exercício Físico , Feminino , Humanos , Menopausa/genética , Estado Pré-Diabético/genética , Estado Pré-Diabético/terapiaRESUMO
OBJECTIVE: Based on the antioxidant effects of taurine, which are capable of controlling oxidative stress in the aging process, the aim of this study was to investigate the effects of taurine supplementation on biomarkers of oxidative stress in women 55 to 70 y of age. METHODS: A double-blind study was conducted with 24 women (61.4 ± 4.2 y, body mass index 31.4 ± 5.1 kg/m²). The participants were randomly assigned to either a control group (GC, n = 11), supplemented with placebo (1.5 g of starch); or a taurine group (GTAU, n = 13), supplemented with taurine (1.5 g), for 16 wk. As primary outcomes, taurine and oxidative stress marker levels were determined in plasma samples. Anthropometry, functional capacity testing, and plasma mineral levels were evaluated as secondary outcomes. The evaluations were performed pre- and postintervention. Food consumption was assessed before, during, and after the intervention. The results were analyzed by two-way repeated analysis of variance measures mixed model, with the Sidak post hoc (P < 0.05). RESULTS: Taurine and superoxide dismutase (SOD, antioxidant enzyme) plasma levels were increased in the GTAU group. SOD levels also were higher than in the GC group after supplementation. Glutathione reductase levels decreased regardless of the intervention. Malondialdehyde levels increased only in the GC participants. CONCLUSION: Taurine supplementation prevented the decrease in the antioxidant enzyme SOD, suggesting taurine as a strategy to control oxidative stress during the aging process.
Assuntos
Antioxidantes , Taurina , Idoso , Biomarcadores , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Malondialdeído , Pessoa de Meia-Idade , Estresse Oxidativo , Superóxido Dismutase , Taurina/farmacologiaRESUMO
Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.
RESUMO
The intensive shift on land cover by anthropogenic activities have led to changes in natural habitats and environmental contamination, which can ultimately impact and threat biodiversity and ecosystem services, such as pollination. The aim of this study was to evaluate the effect of native forest and human-modified land covers on the concentrations of chemical elements accumulated in the neotropical pollinator bee T. angustula. Eight landscapes, within an Ecological Corridor in the State of São Paulo, Brazil, with gradients of forest cover, spatial heterogeneity and varying land covers were used as sampling unities. Bees collected in traps or through actives searches had the concentration of 21 chemical elements determined by ICP-MS. Results show a beneficial effect of forested areas on the concentrations of some well-known toxic elements accumulated in bees, such as Hg, Cd, and Cr. Multivariate Redundancy Analysis (RDA) suggests road as the most important driver for the levels of Cr, Hg, Sb, Al, U, As, Pb and Pt and bare soil, pasture and urban areas as the landscape covers responsible for the concentrations of Zn, Cd, Mn, Mg, Ba and Sr in bees. The results reinforce the potential use of T. angustula bees as bioindicators of environmental quality and also show that these organisms are being directly affected by human land use, offering potential risks for the Neotropical ecosystem. Our study sheds light on how land covers (native forest and human-modified) can influence the levels of contaminants in insects within human-dominated landscapes. The generation of predictions of the levels of toxic metals and metalloids based on land use can both contribute to friendly farming planning as well as to support public policy development on the surrounding of protected areas and biodiversity conservation hotspots.
Assuntos
Abelhas/fisiologia , Monitoramento Ambiental , Metaloides/metabolismo , Metais/metabolismo , Agricultura , Animais , Biodiversidade , Brasil , Ecossistema , Florestas , Intoxicação por Metais Pesados , Humanos , Polinização , SoloRESUMO
Fenamiphos (FS) is a chiral organophosphate pesticide that is used to control nematodes in several crops. Enantioselective differences may be observed in FS activity, bioaccumulation, metabolism, and toxicity. Humans may be exposed to FS through occupational and chronic (food, water, and environmental) exposure. FS may cause undesirable CYP450 pesticide-drug interactions, which may impact human health. Here, the CYP450 isoforms involved in enantioselective FS metabolism were identified, and CYP450 inhibition by rac-FS, (+)-FS, and (-)-FS was evaluated to obtain reliable information on enantioselective FS risk assessment in humans. CYP3A4 and CYP2E1 metabolized FS enantiomers, and CYP2B6 may participate in rac-FS metabolism. In addition, rac-FS, (+)-FS, and (-)-FS were reversible competitive CYP1A2, CYP2C19, and CYP3A4/5 inhibitors. High stereoselective inhibition potential was verified; rac-FS and (-)-FS strongly inhibited and (+)-FS moderately inhibited CYP1A2. Stereoselective differences were also detected for CYP2C19 and CYP3A4/5, which were strongly inhibited by rac-FS, (+)-FS, and (-)-FS. Our results indicated a high potential for CYP450 drug-pesticide interactions, which may affect human health. The lack of stereoselective research on the effect of chiral pesticides on the activity of CYP450 isoforms highlights the importance of assessing the risks of such pesticides in humans.
Assuntos
Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Isoenzimas/metabolismo , Compostos Organofosforados/metabolismo , Praguicidas/metabolismo , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/genética , Interações Medicamentosas , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/química , Isoenzimas/genética , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Compostos Organofosforados/toxicidade , Praguicidas/toxicidade , Proteínas RecombinantesRESUMO
Exposure to high concentrations of cadmium (Cd), widely used in many industries and found in air, food and contaminated water, is not uncommon. Cd damages the cardiovascular system, but the vascular mechanisms involved are not fully understood. This study investigated the mechanisms involved in cardiovascular damage after exposure to high Cd concentrations. Three-month-old male Wistar rats were treated intraperitoneally for 14 days with distilled water (Untreated group) or 1â¯mg/kg cadmium chloride (Cd group). We investigated the systolic blood pressure (SBP) and vascular reactivity of mesenteric resistance arteries (MRA) and the aorta by analysing contractile and relaxation responses in the absence and presence of the endothelium; we also evaluated pathways involved in vascular tone regulation. Superoxide anion production, COX-2 protein expression and in situ detection of COX-2, AT-1, and NOX-1 were evaluated. Oxidative status, creatinine level and angiotensin-converting enzyme (ACE) activity in plasma were also evaluated. Fourteen-day exposure to a high Cd concentration induced hypertension associated with vascular dysfunction in MRA and the aorta. In both vessels, there was increased participation of cyclooxygenase 2 (COX2), angiotensin II type 1 (AT1) receptor and NOX1. MRA also presented endothelial dysfunction, denoted by impaired acetylcholine-mediated relaxation. All vascular changes were accompanied by increased reactive oxygen species production and COX2, NOX1 and AT1 receptor expression in vascular tissue. Overall, high Cd concentrations induced cardiovascular damage: hypertension, endothelial dysfunction and vascular damage in conductance and resistance arteries, NADPH oxidase, renin-angiotensin system and COX2 pathway activation.
Assuntos
Cloreto de Cádmio/toxicidade , Ciclo-Oxigenase 2/metabolismo , Endotélio Vascular/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Hipertensão/induzido quimicamente , NADPH Oxidases/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/enzimologia , Pressão Sanguínea/efeitos dos fármacos , Cloreto de Cádmio/sangue , Relação Dose-Resposta a Droga , Endotélio Vascular/enzimologia , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Poluentes Ambientais/sangue , Hipertensão/enzimologia , Hipertensão/patologia , Hipertensão/fisiopatologia , Injeções Intraperitoneais , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais , Vasoconstrição/efeitos dos fármacosRESUMO
BACKGROUND & AIMS: Although the mechanisms by which statins promote muscle disorders remain unclear, supplementation with dietary antioxidants may mitigate statins' side effects. This study aimed to investigate whether the consumption of Brazil nuts modulates serum creatine kinase (CK) activity in patients regularly using statins. METHODS: The study was performed in the Ribeirão Preto Medical School University Hospital. Thirty-two patients in regular use of statins were divided according to CK activity levels (G1: increased or G2: normal) and received one unit of Brazil nut daily for 3 months. Body composition, blood selenium (Se) concentrations, erythrocyte glutathione peroxidase (GPX) activity, oxidative stress parameters, and CK activity were evaluated before and after supplementation. RESULTS: In both groups, supplementation with one Brazil nut daily for 3 months contributed to achieve decreased levels of CK activity in serum, with positive changes in plasma and erythrocyte Se concentrations (p < 0.0001), and increased levels of GPX activity. Among the parameters related to curbing of oxidative stress, we observed reduced levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in both groups after supplementation. We also found a moderately negative association between CK and GPX activity (r = -41; p < 0.02). Expression of selenoproteins GPX1, SELENOP, and SELENON after Brazil nut supplementation was unchanged. CONCLUSION: Brazil nut consumption enhanced the control of CK activity by improving oxidative stress biomarkers in patients using statins but did not modulate mRNA expression of selenoproteins.
Assuntos
Bertholletia , Creatina Quinase/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Nozes , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , Selenoproteínas/genética , Adolescente , Adulto , Biomarcadores/sangue , Brasil , Feminino , Regulação da Expressão Gênica , Glutationa Peroxidase/sangue , Glutationa Peroxidase/genética , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/sangue , Proteínas Musculares/genética , RNA Mensageiro/sangue , Selenoproteína P/sangue , Selenoproteína P/genética , Selenoproteínas/sangue , Fatores de Tempo , Adulto Jovem , Glutationa Peroxidase GPX1RESUMO
The chiral pesticide fipronil is employed as a racemic mixture to control pests. Although there are no enantioselective differences in the fipronil enantiomer activities toward target organisms, fipronil enantiomers may exhibit enantioselective differences in their bioaccumulation, toxicity, and metabolism toward non-target organisms, including humans. The present work aims to provide significant reliable enantioselective information concerning fipronil risk assessment in humans. For that, the in vitro metabolism of rac-fipronil, S-fipronil, and R-fipronil by human liver microsomes was evaluated, the in vivo enantioselective toxicokinetic parameters were predicted and the main CYP450 isoforms involved in the enantioselective metabolism were determined. The obtained results demonstrated that fipronil may undergo a clearance by the liver and it is exclusively metabolized by the CYP3A4 isoform. Although no significative stereoselective differences were observed, the results provide reliable information on fipronil risk assessment for humans.
Assuntos
Praguicidas/química , Praguicidas/metabolismo , Pirazóis/química , Pirazóis/metabolismo , Citocromo P-450 CYP3A/química , Citocromo P-450 CYP3A/metabolismo , Humanos , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Praguicidas/toxicidade , Pirazóis/toxicidade , Medição de Risco , Estereoisomerismo , ToxicocinéticaRESUMO
In aquatic habitats, metal contamination from natural and anthropogenic sources continues to pose a concern for human and environmental health. Thus, it is important to complete monitoring studies to assess patterns and the extent of metal contamination in these ecosystems. The purpose of this work was to determine the concentrations of 31 chemical elements and water quality parameters of the Todos os Santos River located in the Mucuri Valley, Minas Gerais, Brazil. A multivariate statistical analysis was used to determine any seasonal and spatial patterns from the data. Results demonstrated that metals including Al, Fe, and Ni exceeded Brazilian and international guidelines nutrients as P also exceed water quality standards. Principal components analysis indicated distinct geographical and seasonal patterns for multiple elements with hierarchical cluster analysis confirming the observed spatial patterns of contamination in the Todos os Santos River.
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Metais/análise , Rios/química , Poluentes Químicos da Água/análise , Qualidade da Água , Alumínio/análise , Brasil , Ferro/análise , Análise Multivariada , Níquel/análise , Estações do Ano , Abastecimento de ÁguaRESUMO
New effective compounds for tuberculosis treatment are needed. This study evaluated the effects of a series of quinoxaline-derived chalcones against laboratorial strains and clinical isolates of M. tuberculosis. Six molecules, namely N5, N9, N10, N15, N16, and N23 inhibited the growth of the M. tuberculosis H37Rv laboratorial strain. The three compounds (N9, N15 and N23) with the lowest MIC values were further tested against clinical isolates and laboratory strains with mutations in katG or inhA genes. From these data, N9 was selected as the lead compound for further investigation. Importantly, this chalcone displayed a synergistic effect when combined with moxifloxacin. Noteworthy, the anti-tubercular effects of N9 did not rely on inhibition of mycolic acids synthesis, circumventing important mechanisms of resistance. Interactions with cytochrome P450 isoforms and toxic effects were assessed in silico and in vitro. The chalcone N9 was not predicted to elicit any mutagenic, genotoxic, irritant, or reproductive effects, according to in silico analysis. Additionally, N9 did not cause mutagenicity or genotoxicity, as revealed by Salmonella/microsome and alkaline comet assays, respectively. Moreover, N9 did not inhibit the cytochrome P450 isoforms CYP3A4/5, CYP2C9, and CYP2C19. N9 can be considered a potential lead molecule for development of a new anti-tubercular therapeutic agent.
Assuntos
Antituberculosos/farmacologia , Chalconas/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Proteínas de Bactérias/genética , Catalase/genética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP3A/genética , Sistema Enzimático do Citocromo P-450/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/patogenicidade , Ácidos Micólicos/antagonistas & inibidores , Oxirredutases/genética , Quinoxalinas/farmacologia , Tuberculose/genética , Tuberculose/microbiologia , Tuberculose/patologiaRESUMO
Selenium (Se) is an essential trace element involved in several biological pathways, naturally found in rocks, soils, and food. Even though the daily requirement of Se is achieved through a balanced diet, the use of Se supplements has been frequent. Due to the risk of toxic effects of having Se in excess, supplementation is still under debate. The aim was to evaluate the effects of long-term Se supplementation upon systolic blood pressure (SBP) and redox status of rats exposed to sodium selenite. Male Wistar rats were exposed to 2 and 6 mg/L of sodium selenite in drinking water for 85 days. SBP and body weight were evaluated weekly; oxidative stress biomarkers were measured in blood or plasma; and Se levels were assessed in blood, plasma, kidney, and liver. Se supplementation (2 and 6 mg/L) induced significant increase in the SBP in rats from the 42nd day until the end of the study. This increase on SBP was not associated with significant changes in oxidative stress biomarkers. A significant increase in Se levels was found in whole blood, kidney, and liver from both groups of rats receiving Se supplementation when compared to control. Although the exact mechanisms underlying this augment in SBP are not clear, they are potentially related to other Se biological routes besides the synthesis of selenoproteins, such as GSH-Px. Due to the negative effects upon blood pressure, precautionary measures are advised, since the selling of supplements does not require a medical prescription.
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Peso Corporal/fisiologia , Suplementos Nutricionais , Hipertensão/fisiopatologia , Selenito de Sódio/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Catalase/sangue , Catalase/metabolismo , Glutationa/sangue , Glutationa/metabolismo , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico , Rim/metabolismo , Fígado/metabolismo , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Distribuição Aleatória , Ratos Wistar , Selênio/sangue , Selênio/metabolismo , Selenito de Sódio/efeitos adversos , Fatores de TempoRESUMO
Lead levels (Pb) have been linked to both hyper- and hypo-reactivity of hypothalamic-pituitary-adrenal axis (HPA) axis to acute stress in animals and humans. Similarly, allostatic load (AL), the 'wear and tear' of chronic stress, is associated with inadequate HPA axis activity. We examined whether Pb levels would be associated with altered diurnal cortisol profile, as a primary mediator of AL, during aging. Pb levels were measured from blood samples (BPb) of 126 Brazilian individuals (105 women), between 50 and 82 years old. Six neuroendocrine, metabolic, and anthropometric biomarkers were analyzed and values were transformed into an AL index using clinical reference cut-offs. Salivary samples were collected at home over 2 days at awakening, 30-min after waking, afternoon, and evening periods to determine cortisol levels. A multiple linear regression model showed a positive association between BPb as the independent continuous variable and cortisol awakening response (R2=0.128; B=0.791; p=0.005) and overall cortisol concentration (R2=0.266; B=0.889; p<0.001) as the outcomes. Repeated measures ANOVA showed that individuals with high BPb levels showed higher cortisol at 30min after awakening (p=0.003), and in the afternoon (p=0.002) than those with low BPb values. Regarding AL, regression model showed that BPb was positively associated with AL index (R2=0.100; B=0.204; p=0.032). Correlation analyzes with individual biomarkers showed that BPb was positively correlated with HDL cholesterol (p=0.02) and negatively correlated with DHEA-S (p=0.049). These findings suggest that Pb exposure, even at levels below the reference blood lead level for adults recommended by the National Institute for Occupational Safety and Health and by the Center for Disease Control and Prevention, may contribute to AL and dysregulated cortisol functioning in older adults. Considering these findings were based on cross-sectional data future research is needed to confirm our exploratory results.
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Alostase/efeitos dos fármacos , Síndrome de Cushing/etiologia , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Chumbo/sangue , Chumbo/toxicidade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/efeitos dos fármacos , Biomarcadores/sangue , Brasil , Ritmo Circadiano , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Abstract This study associates blood antioxidants like copper (Cu), manganese (Mn), selenium (Se), zinc (Zn), β-carotene, lycopene and vitamins (A and E) to sociodemographic features and seasonality in communities from the Tapajós River region, Brazilian Amazon. We observed increased Mn, Se and Zn levels compared to the average Brazilian population, whereas this is only the case for β-carotene in the rainy season. Lycopene levels fall within the reference range, although lower than those found in other Brazilian regions. Cu, Se, Zn, β-carotene, lycopene and vitamin E levels vary among seasons. β-carotene, Mn and Se vary among communities. Se and Zn vary with smoking habits and sex, respectively. In addition, β-carotene and vitamins (A and E) are altered by alcohol consumption. Villagers who both farmed and fished present higher Cu and lower β-carotene levels than participants with a single occupation. Vitamin E levels depend upon the individual state of origin. These data provide important baseline information for antioxidant status in this Amazonian riparian population.
Resumo O presente estudo reporta as concentrações plasmáticas dos antioxidantes cobre (Cu), manganês (Mn), selênio (Se), zinco (Zn), β-caroteno, licopeno e vitaminas (A e E) em moradores da região do Rio Tapajós, Pará, Amazônia, e as relaciona com características sociodemográficas e sazonalidade (seca e cheia). Os teores de Mn, Se e Zn foram acima dos valores de referência (VR) e daqueles achados em outras regiões do Brasil, enquanto para o β-caroteno tal achado ocorreu apenas na estação da cheia. Os valores de licopeno foram dentro dos VR, porém abaixo dos achados em outras regiões do Brasil. Os níveis de Cu, Se, Zn, β-caroteno, licopeno e vitamina E variaram entre as estações. Variação intercomunitária foi constatada para β-caroteno, Mn e Se. Os teores de Se e Zn foram alterados, respectivamente, por tabagismo e sexo. Os níveis de β-caroteno e vitaminas (A e E) alteraram-se com o consumo de bebida alcoólica. A vitamina E foi dependente do estado de origem. Participantes que desempenhavam ambas as profissões de agricultor e pescador apresentavam teores de Cu superiores e de β-caroteno inferiores comparativamente àqueles que desempenhavam uma única profissão. Esses dados fornecem informações sobre os teores de antioxidantes para essa população amazônica.