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1.
Clin Obes ; : e12688, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943556

RESUMO

Obesity increases serum triglycerides and decreases high-density lipoprotein cholesterol (HDL-C). The objective is to explore some functions of HDL, cholesterol transfers and antioxidant, in subjects with grade I (G1-OB) and III (G3-OB) obesity and effects of bariatric surgery on G3-OB. Fifteen G3-OB patients (43 ± 6 years, BMI 49 ± 3 kg/m2) were studied before and 1 year after bariatric surgery; 15 G1-OB (32 ± 2 years, 32 ± 2 kg/m2) and 15 normal weight (NW) (38 ± 6 years, 22 ± 1 kg/m2) were also studied. HDL diameter, cholesterol transfer to HDL and antioxidant capacity of HDL were determined. G3-OB had higher triglycerides and lower HDL-C; G1-OB had higher triglycerides than NW but HDL-C was equal. Compared to NW, HDL size was smaller in G3-OB but equal in G1-OB. One year after bariatric surgery, BMI and triglycerides of G3-OB decreased (p < .0001 and p = .0012, respectively) and HDL-C increased (p < .0001), equalling of NW group. Antioxidant capacity and cholesterol transfers were not different in groups and were unchanged 1 year after bariatric surgery in G3-OB. HDL antioxidant capacity and transfer of cholesterol to HDL were not defective in obesity despite HDL-C reduction and smaller HDL size. In addition, pronounced weight loss by bariatric surgery did not change those protective functions.

2.
Exp Cell Res ; 430(1): 113715, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37429373

RESUMO

In cancer, cell migration contributes to the spread of tumor cells resulting in metastasis. Heterogeneity in the migration capacity can produce individual cells with heightened capacity leading to invasion and metastasis. Our hypothesis is that cell migration characteristics can divide asymmetrically in mitosis, allowing a subset of cells to have a larger contribution to invasion and metastasis. Therefore, our aim is to elucidate whether sister cells have different migratory capacity and analyze if this difference is defined by mitosis. Through time-lapse videos, we analyzed migration speed, directionality, maximum displacement of each trajectory, and velocity as well as cell area and polarity and then compared the values between mother-daughter cells and between sister cells of three tumor cell lines (A172, MCF7, SCC25) and two normal cell lines (MRC5 and CHO·K1 cells). We observed that daughter cells had a different migratory phenotype compared to their mothers, and one single mitosis is enough for the sisters behave like nonrelated cells. However, mitosis did not influence cell area and polarity dynamics. These findings indicates that migration performance is not heritable, and that asymmetric cell division might have an important impact on cancer invasion and metastasis, by producing cells with different migratory capacity.


Assuntos
Mitose , Células-Tronco , Movimento Celular , Divisão Celular Assimétrica , Linhagem Celular Tumoral
3.
ACS Chem Neurosci ; 14(16): 2857-2867, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37499207

RESUMO

Oxidative glutamate toxicity is regarded as one of the injurious mechanisms associated with ischemic stroke, which represents a major health problem and requires improved pharmacological treatments. We designed and synthesized two new probucol analogues [2,6-di-tert-butyl-4-selenocyanatophenol (C1) and 4,4'-diselanediylbis (2,6-di-tert-butylphenol) (C2)] and investigated their effects against glutamate-induced neuronal oxidative toxicity in vitro in cultured HT22 cells, compared with their parental compound (probucol). In addition, C2, which exhibited the lowest toxicity, was investigated in an in vivo rodent model of ischemic stroke. Glutamate caused concentration- and time-dependent cytotoxicity in HT22 neuronal cells, which was preceded by increased levels of oxidants and depletion of the antioxidant glutathione. The analogues (C1 and C2), but not probucol, significantly decreased the levels of oxidants (including mitochondrial superoxide anion and lipid reactive oxygen species (ROS)) and protected against glutamate-induced cytotoxicity. In the in vivo model of ischemic stroke, which was based on central injections of the vasoconstrictor agent endothelin-1 (800 pmol/site), C2 (20 or 50 mg/kg/day, intraperitoneally, for 4 consecutive days after stroke) displayed significant beneficial effects against ischemic injury in vivo, improving rats' motor-related behavioral skills and decreasing stroke-related striatal gliosis. This is the first study to design, synthesize, and present a probucol analogue (C2) with in vivo beneficial effects against ischemic stroke. This novel compound, which was able to mitigate glutamate-induced oxidative toxicity in vitro, represents a promising neuroprotective drug.


Assuntos
AVC Isquêmico , Fármacos Neuroprotetores , Ratos , Animais , Probucol/farmacologia , Neuroproteção , Ácido Glutâmico/toxicidade , Roedores , Estresse Oxidativo , Fármacos Neuroprotetores/farmacologia , Oxidantes/farmacologia
4.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36769233

RESUMO

Neuron-glia interactions are essential for the central nervous system's homeostasis. Microglial cells are one of the key support cells in the brain that respond to disruptions in such homeostasis. Although their participation in neuroinflammation is well known, studies investigating their role in ferroptosis, an iron-dependent form of nonapoptotic cell death, are lacking. To address this issue, we explored whether microglial (BV-2 cells) activation products can intensify, mitigate or block oxidative and/or ferroptotic damage in neuronal cells (HT22 cell line). Cultured BV-2 microglial cells were stimulated with 5-100 ng/mL lipopolysaccharide (LPS) for 24 h and, after confirmation of microglial activation, their culture medium (conditioned media; CM) was transferred to neuronal cells, which was subsequently (6 h later) exposed to glutamate or tert-butyl hydroperoxide (t-BuOOH). As a major finding, HT22 cells pretreated for 6 h with CM exhibited a significant ferroptosis-resistant phenotype characterized by decreased sensitivity to glutamate (15 mM)-induced cytotoxicity. However, no significant protective effects of LPS-activated microglial cell-derived CM were observed in t-BuOOH (30 µM)-challenged cells. In summary, activated microglia-derived molecules may protect neuronal cells against ferroptosis. The phenomenon observed in this work highlights the beneficial relationship between microglia and neurons, highlighting new possibilities for the control of ferroptosis.


Assuntos
Ferroptose , Microglia , Microglia/metabolismo , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Ácido Glutâmico/toxicidade , Ácido Glutâmico/metabolismo , Células Cultivadas , Neurônios/metabolismo
5.
Environ Sci Pollut Res Int ; 28(17): 21730-21741, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33411293

RESUMO

Uruguay River is the most important river in western Rio Grande do Sul, separating Brazil from Argentina and Uruguay. However, its pollution is of great concern due to agricultural activities in the region and the extensive use of pesticides. In a long term, this practice leads to environmental pollution, especially to the aquatic system. The objective of this study was to analyze the physicochemical characteristics, metals and pesticides levels in water samples obtained before and after the planting and pesticides' application season from three sites: Uruguay River and two minor affluents, Mezomo Dam and Salso Stream. For biomonitoring, the free-living nematode Caenorhabditis elegans was used, which were exposed for 24 h. We did not find any significant alteration in physicochemical parameters. In the pre- and post-pesticides' samples we observed a residual presence of three pesticides (tebuconazole, imazethapyr, and clomazone) and metals which levels were above the recommended (As, Hg, Fe, and Mn). Exposure to both pre- and post-pesticides' samples impaired C. elegans reproduction and post-pesticides samples reduced worms' survival rate and lifespan. PCA analysis indicated that the presence of metals and pesticides are important variables that impacted C. elegans biological endpoints. Our data demonstrates that Uruguay River and two affluents are contaminated independent whether before or after pesticides' application season. In addition, it reinforces the usefulness of biological indicators, since simple physicochemical analyses are not sufficient to attest water quality and ecological safety.


Assuntos
Praguicidas , Poluentes Químicos da Água , Animais , Argentina , Monitoramento Biológico , Brasil , Caenorhabditis elegans , Monitoramento Ambiental , Praguicidas/análise , Praguicidas/toxicidade , Rios , Uruguai , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
6.
Environ Pollut ; 256: 113406, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31662251

RESUMO

Toluene is a highly volatile organic solvent present in gasoline. Exposure mainly occurs by absorption via the pulmonary tract and easily reaches the central nervous system, which causes toxic effects. Toluene toxicity has been described but not well established. The present work aimed to evaluate the effects of airborne exposure to toluene, the in vivo model Caenorhabditis elegans was assessed to determine whether nematode could be used to evaluate the effects of exposure to toluene and the possible mechanisms of toxicity of the solvent. Worms at the first or fourth larval stages were exposed to toluene for 48 or 24 h, respectively, in a laboratory-developed vapor chamber at concentrations of 450, 850, 1250 and 1800 ppm. We observed increases in worm mortality and significant developmental delays that occurred in a concentration-dependent manner. An increased incidence of apoptotic events in treated germline cells was shown, which was consistent with observed reductions in reproductive capacity. In addition, toluene promoted significant behavioural changes affecting swimming movements and radial locomotion, which were associated with changes in the fluorescence intensity and morphology of GABAergic and cholinergic neurons. We conclude that toluene exposure was toxic to C. elegans, with effects produced by the induction of apoptosis and neuronal damage.


Assuntos
Poluentes Atmosféricos/toxicidade , Caenorhabditis elegans/fisiologia , Tolueno/toxicidade , Poluentes Atmosféricos/análise , Animais , Apoptose/fisiologia , Caenorhabditis elegans/efeitos dos fármacos , Células Germinativas , Larva/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Tolueno/análise
7.
Biol Cell ; 110(10): 225-236, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30157294

RESUMO

BACKGROUND INFORMATION: Cell migration requires the coordinated activation of structural and signalling molecules, such as the RhoGTPase Rac1. It is known that the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex assembly, which generates reactive oxygen species (ROS) at the cell membrane, also relies on Rac1 activation, indicating a possible effect of ROS during cell migration. In this study, we evaluated the effect of NADPH-oxidase-derived ROS on the migration process. RESULTS: Using time-lapse videos of CHO.K1 cells plated on fibronectin (2 µg/ml) or collagen (5 µg/cm2 ), we observed that depletion of ROS by N-acetyl-cysteine (NAC, 10 mM), an unspecific antioxidant, or diphenyliodonium (DPI, 10 µM), a NADPH-oxidase inhibitor, induced a ∼50% decrease in migration speed and severely impacted migration directionality. Then, we analysed the effects of NADPH oxidase on three migratory events: protrusion rate, adhesion process and signalling pathways related to cell migration. DPI induced an increase of ∼3 protrusion/cell, which were 2× faster but had a ∼50% retraction when compared with control. By pull-down assay, we observed no changes on Rac1 activation, indicating that ROS-mediated effects were related to downstream molecules, such as adhesion-related molecules. A reduction of the adhesion marker FAK-Y397 levels in cells treated with NAC and DPI was observed. In order to analyse adhesion dynamics, CHO.K1 cells transfected with paxillin-GFP analysed with total internal reflectance fluorescence (TIRF) indicated that DPI (5 µM) induced larger adhesions when compared with control. CONCLUSION: These results indicate that the local generation of NADPH-oxidase-derived ROS can modulate cell migration due to changes on adhesion dynamics and signalling. SIGNIFICANCE: This study highlights the physiological requirement of ROS for cell migration and the potential use of these molecules as targets to modulate the cell migration process at different diseases.


Assuntos
Adesão Celular , Movimento Celular , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Compostos de Bifenilo , Células CHO , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Cricetulus , Oniocompostos , Transdução de Sinais/efeitos dos fármacos
8.
Chemosphere ; 149: 391-9, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26881336

RESUMO

Magellanic penguins, Spheniscus magellanicus, are the most abundant penguins living in temperate regions of South America and are good indicators of environmental pollution in the region. Persistent organic pollutants (POPs) were detected in the liver of Magellanic penguins found debilitated or dead on the beaches of Brazil (states of Rio de Janeiro, Sao Paulo, Santa Catarina and Rio Grande do Sul) between 2008 and 2012 as well as in Uruguay and Chile in 2011. Polychlorinated biphenyls (PCBs) were more prevalent than organochlorine pesticides (DDTs ∼ HCB ∼ Drins) and polybrominated diphenyl ethers (PBDEs). Among PCBs, penta-, hexa- and hepta-chlorinated congeners were predominant. Concentrations of POPs were similar between the Pacific and Atlantic penguin populations, except for PCBs, which were relatively higher in the Pacific population. During the study years (2008-2012), large variations were found in organochlorine pesticides and PCBs tended to decline. Overall, the southern portion of South America has low concentrations of POPs, with either a constant trend or evidence of decline.


Assuntos
Monitoramento Ambiental , Spheniscidae/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Brasil , Chile , Éteres Difenil Halogenados/metabolismo , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/metabolismo , Fígado/química , Fígado/metabolismo , Praguicidas/análise , Praguicidas/metabolismo , Bifenilos Policlorados/análise , Bifenilos Policlorados/metabolismo , América do Sul , Uruguai
9.
Rev. bras. med. esporte ; Rev. bras. med. esporte;20(3): 190-194, May-Jun/2014. tab, graf
Artigo em Português | LILACS | ID: lil-718422

RESUMO

INTRODUÇÃO: Embora estudos demonstrem a importância da atividade física na prevenção e manutenção de um padrão de vida saudável, a prática pode determinar um aumento no risco da ocorrência de lesões entre aqueles praticantes de atividades desportivas. OBJETIVO: Determinar a prevalência e os fatores associados à ocorrência de lesões durante a prática de atividade física no tempo de lazer na cidade de Pelotas, RS, Brasil. MÉTODOS: Estudo transversal de base populacional realizado na área urbana do município de Pelotas, RS, Brasil. Uma amostra levando em consideração os diversos conglomerados foi selecionada. Características sociodemográficas, econômicas, comportamentais, nutricionais e relacionadas à ocorrência de lesões durante a prática de atividade física foram coletadas por meio de questionário padronizado e pré-codificado. RESULTADOS: O percentual de lesões em sujeitos praticantes de atividade física no lazer foi de 21,9% (IC95% 18,3 - 25,9). As lesões mais prevalentes foram contusões (39,6%), luxações (30,2%) e distensões (11,3%) e a prática de futebol e musculação foram as atividades onde mais ocorreram lesões. As lesões estiveram associadas ao sexo masculino, idades mais jovens e a indivíduos de cor da pele preta e parda. CONCLUSÃO: Embora a prevalência de lesões entre praticantes seja importante, os benefícios decorrentes de um estilo de vida ativo superam os riscos. .


INTRODUCTION: Although studies show the importance of physical activity in prevention and maintaining a healthy standard of living, its practice can determine an increased risk of occurrence of injuries among people who practice sports activities. OBJECTIVE: Determine the prevalence and factors associated with injuries during leisure-time physical activity practice in the city of Pelotas, RS, Brazil. METHODS: Population-based cross-sectional study conducted in the urban area of Pelotas, southern Brazil. A sample taking into account the different clusters was selected. Sociodemographic, economic, behavioral, nutritional and physical activity injury related characteristics were collected using a standardized and pre-coded questionnaire. RESULTS: The prevalence of injuries in subjects physically active during leisure time was 21.9% (CI95% 18.3 - 25.9). The most prevalent injuries were contusions (39.6%), dislocations (30.2%) and sprains (11.3%) and soccer practice and weightlifting were activities where more injuries occurred. The injuries were associated with male gender, younger age and black and mixed race. CONCLUSION: Although the prevalence of injuries among practitioners is important, the benefits of an active lifestyle outweigh the risks. .


INTRODUCCIÓN: Aunque estudios demuestren la importancia de la actividad física en la prevención y mantenimiento de un estándar de vida saludable, la práctica puede determinar un aumento en el riesgo de la ocurrencia de lesiones entre aquellos practicantes de actividades deportivas. OBJETIVO: Determinar la prevalencia y los factores asociados a la ocurrencia de lesiones durante la práctica de actividad física en el tiempo libre en la ciudad de Pelotas, RS, Brazil. MÉTODOS: Estudio transversal de base poblacional realizado en el área urbana del municipio de Pelotas, RS, Brazil. Fue seleccionada una muestra llevando en consideración los diversos conglomerados. Fueron colectadas características sociodemográficas, económicas, comportamentales, nutricionales y relacionadas a la ocurrencia de lesiones durante la práctica de actividad física por medio de cuestionario estandarizado e precodificado. RESULTADOS: El porcentual de lesiones en sujetos practicantes de actividad física en su tiempo libre fue de 21,9% (IC95% 18,3 - 25,9). Las lesiones más prevalentes fueron contusiones (39,6%), luxaciones (30,2%) y distensiones (11,3%) y la práctica de fútbol y musculación fueron las actividades en donde más ocurrieron lesiones. Las lesiones estuvieron asociadas al sexo masculino, edades más jóvenes y a individuos con color de piel negra y parda. CONCLUSIÓN: Aunque la prevalencia de lesiones entre practicantes sea importante, los beneficios provenientes de un estilo de vida activo superan los riesgos. .

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