Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Food Chem Toxicol ; 133: 110766, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31430511

RESUMO

People with large amounts of adipose tissue are more vulnerable and more likely to develop diseases where oxidative stress and inflammation play a pivotal role, than persons with a healthy weight. Atmospheric contamination is a reality to which a large part of the worldwide population is exposed. Half of today's global electrical energy is derived from coal. Each organism, in its complexity, responds in different ways to dietary compounds and air pollution. The objective of this study was to investigate the effects of obesity and coal ash inhalation within the parameters of oxidative damage and inflammation in different regions of the brain of rats. A diet containing high-fat concentration was administered chronically to rats, along with exposure to coal ash, simulating the contamination that occurs daily throughout human life. High-resolution transmission electron microscopy was performed to identify the particles present in coal ash samples. Our results demonstrated that obese rats exposed to coal ash inhalation were more affected by oxidative damage with subsequent systemic inflammation in the hippocampus. Since there is an inflammatory predisposition caused by obesity, the inhalation of nanoparticles increases the levels of free radicals, resulting in systemic inflammation and oxidative damage, which can lead to chronic neurodegeneration.


Assuntos
Cinza de Carvão/toxicidade , Hipocampo/efeitos dos fármacos , Inflamação/metabolismo , Exposição por Inalação , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poluentes Atmosféricos/toxicidade , Animais , Catalase/metabolismo , Dieta Hiperlipídica , Glutationa Peroxidase/metabolismo , Inflamação/induzido quimicamente , Masculino , Ratos Wistar , Superóxido Dismutase/metabolismo
2.
Int J Dev Neurosci ; 78: 210-214, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31330240

RESUMO

Maple Syrup Urine Disease (MSUD) is an inborn error of the metabolism caused by defects in the branched a-ketoacid dehydrogenase complex (BCKDC), leading to the accumulation of branched chain amino acids (BCAAs) (leucine, isoleucine and valine). Patients with MSUD present a series of neurological dysfunction. Recent studies have been associated the brain damage in the MSUD with inflammation and immune system activation. MSUD patients die within a few months of life due to recurrent metabolic crises and neurologic deterioration, often precipitated by infection or other stresses. In this regard, our previous results showed that the inflammatory process, induced by lipopolysaccharide (LPS), associated with high levels of BCAAs causes blood-brain barrier (BBB) breakdown due to hyperactivation of MMPs. Thus, we hypothesize that the synergistic action between high concentrations of BCAAs (H-BCAAs) and LPS on BBB permeability and hyperactivation of MMPs could be through an increase in the production of cytokines and RAGE protein levels. We observed that high levels of BCAA in infant rats are related to increased brain inflammation induced by LPS administration. In addition, BCAA exposure led to an increase on brain RAGE expression of young rats. The brain inflammation was characterized by enhanced levels of interleukin 1 ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and Interferon- γ (IFN-γ), and decreased content of interleukin-10 (IL-10). Therefore, MSUD is associated with a more intense neuroinflammation induced by LPS infection.

3.
Neurochem Int ; 124: 114-122, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30639195

RESUMO

OBJECTIVE: Some factors related to lifestyle, including stress and high-fat diet (HFD) consumption, are associated with higher prevalence of obesity. These factors can lead to an imbalance between ROS production and antioxidant defenses and to mitochondrial dysfunctions, which, in turn, could cause metabolic impairments, favoring the development of obesity. However, little is known about the interplay between these factors, particularly at early ages, and whether long-term sex-specific changes may occur. Here, we evaluated whether social isolation during the prepubertal period only, associated or not with chronic HFD, can exert long-term effects on oxidative status parameters and on mitochondrial function in the whole hypothalamus, in a sex-specific manner. METHODS: Wistar male and female rats were divided into two groups (receiving standard chow or standard chow + HFD), that were subdivided into exposed or not to social isolation during the prepubertal period. Oxidative status parameters, and mitochondrial function were evaluated in the hypothalamus in the adult age. RESULTS: Regarding antioxidant enzymes activities, HFD decreased GPx activity in the hypothalamus, while increasing SOD activity in females. Females also presented increased total thiols; however, non-protein thiols were lower. Main effects of stress and HFD were observed in TBARS levels in males, with both factors decreasing this parameter. Additionally, HFD increased complex IV activity, and decreased mitochondrial mass in females. Complex I-III activity was higher in males compared to females. CONCLUSION: Stress during the prepubertal period and chronic consumption of HFD had persistent sex-specific effects on oxidative status, as well as on its consequences for the cell and for mitochondrial function. HFD had more detrimental effects on females, inducing oxidative imbalance, which resulted in damage to the mitochondria. This HFD-induced imbalance may be related to the development of obesity.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Hipotálamo/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Caracteres Sexuais , Estresse Psicológico/metabolismo , Animais , Feminino , Masculino , Potenciais da Membrana/fisiologia , Ratos , Ratos Wistar , Maturidade Sexual/fisiologia , Estresse Psicológico/psicologia
4.
Neurotoxicology ; 69: 164-180, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30316701

RESUMO

Fish consumption and ubiquitous methylmercury (MeHg) exposure represent a public health problem globally. Micronutrients presented in fish affects MeHg uptake/distribution. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. The present study aimed to examine the effects of both MeHg and retinyl palmitate administered to pregnant and lactating rats. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/Kg/day) and retinyl palmitate (7500 µg RAE1/Kg/day), either individually or in combination from the gestational day 0 to weaning. In dams, maternal behavior was scored. In neonatal and infant offspring, associative learning and neurodevelopment were evaluated. Further periadolescent male and female pups were assessed for open field, habituation and object recognition using episodic-like memory paradigm. Maternal and offspring redox parameters were evaluated. Our results showed no effects of MeHg-VitA co-administration in the quality of maternal care but showed subtle alterations in the pro-oxidant response of the hippocampus. In offspring, MeHg-VitA co-exposure affected early associative learning in neonatal pups, with no further modifications in neurodevelopment, and no locomotor or exploratory alterations in later developmental stages. Habituation was altered in a sex-dependent manner, but no overall memory disturbances were encountered. Finally, MeHg-VitA co-administration reduced lipoperoxidation in male offspring hippocampus. In conclusion, VitA co-administration in dams, under our exposure protocol, can counteract the deleterious neurodevelopmental effects solely attributed to low-dose MeHg in a tissue-specific mechanism, suggesting a protective effect of VitA against MeHg-induced oxidative damage in the central nervous system, especially in the offspring. Further work is needed to confirm our findings and elucidate the molecular mechanisms of MeHg-VitA modulation. Pre-clinical assays are necessary to demonstrate the potential therapeutical use of VitA in populations directly or indirectly exposed to MeHg.


Assuntos
Lactação/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Compostos de Metilmercúrio/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Vitamina A/análogos & derivados , Animais , Anticarcinógenos/administração & dosagem , Aprendizagem por Associação/efeitos dos fármacos , Aprendizagem por Associação/fisiologia , Diterpenos , Combinação de Medicamentos , Feminino , Lactação/fisiologia , Locomoção/fisiologia , Masculino , Compostos de Metilmercúrio/toxicidade , Odorantes , Estresse Oxidativo/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Vitamina A/administração & dosagem
5.
Phytother Res ; 32(12): 2466-2474, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30277282

RESUMO

Microbiota alterations are observed in pathological conditions, and their regulation is a subject of great interest. Gut microbes are affected by diet, and plant polyphenols may have positive effect on gut microbiota; however, plant-derived extracts may have toxic effects. Guarana (Paullinia cupana Mart.) is a nontraditional medicinal plant applied worldwide. Guarana yields an alkaloid and polyphenol-rich seed with antimicrobial, antioxidant, and anti-inflammatory properties, where caffeine is the major compound. We evaluated the effects of guarana seed powder (GSP) and purified caffeine on gut microbial composition and redox and inflammatory parameters in Wistar rats after 21 days of treatment. Fecal microbiota was analyzed utilizing 16S rDNA sequencing. Antioxidant enzymes activities from liver, kidney, and colon, as well as oxidative damage markers, were evaluated. Total nonenzymatic antioxidant potential was also evaluated. Microbiota was altered by both treatments, GSP and caffeine, without loss of diversity. In the liver, the kidney, and the colon, we observed a decrease in the antioxidant enzymes activities in the GSP group with no increase in the expression of oxidative damage markers, although some enzymes were also regulated by caffeine. Taken together, these results suggested that GSP ameliorates redox parameters but negatively affected gut microbiota, partially via caffeine.


Assuntos
Cafeína/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Teobromina/farmacologia , Teofilina/farmacologia , Animais , Antioxidantes/farmacologia , Cafeína/química , Disbiose/induzido quimicamente , Disbiose/microbiologia , Disbiose/patologia , Masculino , Oxirredução/efeitos dos fármacos , Paullinia/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Ratos , Ratos Wistar , Sementes , Teobromina/química , Teofilina/química
6.
Comput Biol Chem ; 72: 62-76, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29414098

RESUMO

The genes of the NFκB pathway are involved in the control of a plethora of biological processes ranking from inhibition of apoptosis to metastasis in cancer. It has been described that Gliobastoma multiforme (GBM) patients carry aberrant NFκB activation, but the molecular mechanisms are not completely understood. Here, we present a NFκB pathway analysis in tumor specimens of GBM compared to non-neoplasic brain tissues, based on the different kind of cycles found among genes of a gene co-expression network constructed using quantized data obtained from the microarrays. A cycle is a closed walk with all vertices distinct (except the first and last). Thanks to this way of finding relations among genes, a more robust interpretation of gene correlations is possible, because the cycles are associated with feedback mechanisms that are very common in biological networks. In GBM samples, we could conclude that the stoichiometric relationship between genes involved in NFκB pathway regulation is unbalanced. This can be measured and explained by the identification of a cycle. This conclusion helps to understand more about the biology of this type of tumor.


Assuntos
Retroalimentação Fisiológica , Glioblastoma/genética , NF-kappa B/metabolismo , Transdução de Sinais/genética , Ciclo Celular/genética , Ciclo Celular/fisiologia , Curadoria de Dados , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/fisiologia , Glioblastoma/fisiopatologia , Humanos , Análise em Microsséries , NF-kappa B/genética , Transdução de Sinais/fisiologia
7.
Biochim Biophys Acta ; 1852(1): 120-30, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25445541

RESUMO

Glioma cells release cytokines to stimulate inflammation that facilitates cell proliferation. Here, we show that Lipopolysaccharide (LPS) treatment could induce glioma cells to proliferate and this process was dependent on nucleotide receptor activation as well as interleukin-8 (IL-8/CXCL8) secretion. We observed that extracellular nucleotides controlled IL-8/CXCL8 and monocyte chemoattractant protein 1 (MCP-1/CCL2) release by U251MG and U87MG human glioma cell lines via P2X7 and P2Y6 receptor activation. The LPS-induced release of these cytokines was also modulated by purinergic receptor activation since IL-8 and MCP-1 release was decreased by the nucleotide scavenger apyrase as well as by the pharmacological P2Y6 receptor antagonists suramin and MRS2578. In agreement with these observations, the knockdown of P2Y6 expression decreased LPS-induced IL-8 release as well as the spontaneous release of IL-8 and MCP-1, suggesting an endogenous basal release of nucleotides. Moreover, high millimolar concentrations of ATP increased IL-8 and MCP-1 release by the glioma cells stimulated with suboptimal LPS concentration which were blocked by P2X7 and P2Y6 antagonists. Altogether, these data suggest that extracellular nucleotides control glioma growth via P2 receptor-dependent IL-8 and MCP-1 secretions.


Assuntos
Neoplasias Encefálicas/metabolismo , Proliferação de Células , Quimiocina CCL2/metabolismo , Glioma/metabolismo , Interleucina-8/metabolismo , Receptores Purinérgicos/fisiologia , Sequência de Bases , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Primers do DNA , Glioma/patologia , Humanos , Reação em Cadeia da Polimerase , Receptores Purinérgicos/genética , Receptores Purinérgicos/metabolismo , Transdução de Sinais
8.
ScientificWorldJournal ; 2014: 696485, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24587745

RESUMO

Chemoreception is among the most important sensory modalities in animals. Organisms use the ability to perceive chemical compounds in all major ecological activities. Recent studies have allowed the characterization of chemoreceptor gene families. These genes present strikingly high variability in copy numbers and pseudogenization degrees among different species, but the mechanisms underlying their evolution are not fully understood. We have analyzed the functional networks of these genes, their orthologs distribution, and performed phylogenetic analyses in order to investigate their evolutionary dynamics. We have modeled the chemosensory networks and compared the evolutionary constraints of their genes in Mus musculus, Homo sapiens, and Rattus norvegicus. We have observed significant differences regarding the constraints on the orthologous groups and network topologies of chemoreceptors and signal transduction machinery. Our findings suggest that chemosensory receptor genes are less constrained than their signal transducing machinery, resulting in greater receptor diversity and conservation of information processing pathways. More importantly, we have observed significant differences among the receptors themselves, suggesting that olfactory and bitter taste receptors are more conserved than vomeronasal receptors.


Assuntos
Células Quimiorreceptoras/metabolismo , Evolução Molecular , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais/genética , Análise de Variância , Animais , Análise por Conglomerados , Biologia Computacional , Ontologia Genética , Humanos , Camundongos , Modelos Genéticos , Filogenia , Ratos , Receptores Acoplados a Proteínas-G/metabolismo , Especificidade da Espécie
9.
PLoS One ; 8(12): e82457, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24349289

RESUMO

Neuroblastoma is the most common extracranial tumor and a major cause of infant cancer mortality worldwide. Despite its importance, little is known about its molecular mechanisms. A striking feature of this tumor is its clinical heterogeneity. Possible outcomes range from aggressive invasion to other tissues, causing patient death, to spontaneous disease regression or differentiation into benign ganglioneuromas. Several efforts have been made in order to find tumor progression markers. In this work, we have reconstructed the neuroblastoma regulatory network using an information-theoretic approach in order to find genes involved in tumor progression and that could be used as outcome predictors or as therapeutic targets. We have queried the reconstructed neuroblastoma regulatory network using an aggressive neuroblastoma metastasis gene signature in order to find its master regulators (MRs). MRs expression profiles were then investigated in other neuroblastoma datasets so as to detect possible clinical significance. Our analysis pointed MAX as one of the MRs of neuroblastoma progression. We have found that higher MAX expression correlated with favorable patient outcomes. We have also found that MAX expression and protein levels were increased during neuroblastoma SH-SY5Y cells differentiation. We propose that MAX is involved in neuroblastoma progression, possibly increasing cell differentiation by means of regulating the availability of MYC:MAX heterodimers. This mechanism is consistent with the results found in our SH-SY5Y differentiation protocol, suggesting that MAX has a more central role in these cells differentiation than previously reported. Overexpression of MAX has been identified as anti-tumorigenic in other works, but, to our knowledge, this is the first time that the link between the expression of this gene and malignancy was verified under physiological conditions.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Neuroblastoma/genética , Neuroblastoma/patologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Linhagem Celular Tumoral , Análise por Conglomerados , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Modelos Biológicos , Neuroblastoma/metabolismo , Neuroblastoma/mortalidade , Transdução de Sinais , Células Tumorais Cultivadas
10.
Chem Biodivers ; 10(4): 507-23, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23576339

RESUMO

Satureja hortensis L. is an aromatic plant with antibacterial and antibiofilm activities against periodontopathogens. Here, we attempted to find out whether the antioxidant properties of S. hortensis L. essential oil (EO) could be used to inhibit matrix metalloproteinase (MMP) activities and prevent the induction of cell death by a pro-oxidant insult. First, a landscape analysis of MMP and REDOX/nitric oxide (NO)-related genes was performed (MRN model), and array data from periodontitis patients were plotted over the newly developed model. Thereafter, the antigelatinolytic activity of S. hortensis L. EO and its preventive effect against hydrogen peroxide (H2 O2 )-induced cell death were tested in vitro (HaCaT cells). Up-regulation of MMP genes in the MRN network (except for MMP-10, -15, -16, -20, -25, and -26) and differential expression of genes coding for antioxidant enzymes were found among others in periodontitis samples. MMP2 and MMP9 were central genes in the MRN network model. Moreover, treatments with 1 and 5 µl/ml of S. hortensis L. EO inhibited both MMP-2 and MMP-9 activities, and H2 O2 -induced cell death in vitro. We concluded that S. hortensis L. EO could be a promising host-modulating agent, since oxidative stress and excessive MMP expression/activity are typical hallmarks of periodontal pathogenesis.


Assuntos
Antioxidantes/química , Inibidores de Metaloproteinases de Matriz/química , Metaloproteinases da Matriz/química , Óxido Nítrico/metabolismo , Óleos Voláteis/química , Periodontite/metabolismo , Satureja/química , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular , Redes Reguladoras de Genes , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/toxicidade , Metaloproteinase 2 da Matriz/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Testes de Sensibilidade Microbiana , Modelos Moleculares , Óleos Voláteis/farmacologia , Oxirredução , Periodontite/tratamento farmacológico , Periodontite/patologia , Regulação para Cima/efeitos dos fármacos
11.
J. physiol. biochem ; 68(3): 365-375, sept. 2012.
Artigo em Inglês | IBECS | ID: ibc-122325

RESUMO

Heat shock protein 70 (HSP70) is a chaperone that maintains protein conformation during heat stress. It has recently been observed that HSP70 may be released from cells in response to increased energy demand (e.g., exercise) and/or oxidative stress. Since HSP70 levels should change in response to athletic training, we have investigated whether blood HSP70 levels in young women handball players change over a complete training season. Thirty women handball players (12–24 years old) were divided into (..) (AU)


Assuntos
Humanos , Feminino , Proteínas de Choque Térmico HSP70 , Condicionamento Físico Humano/fisiologia , Estradiol/sangue , Esportes/fisiologia , Mediadores da Inflamação/análise , Inflamação/fisiopatologia , Estresse Oxidativo/fisiologia
12.
Rev. colomb. psiquiatr ; 40(supl.1): 166-182, oct. 2011. ilus, graf, tab
Artigo em Inglês | LILACS-Express | ID: lil-636534

RESUMO

Bipolar disorder (BD) is a chronic major mental illness characterized by extreme mood episodes, cognitive impairment, and high rates of disability. Several lines of evidence suggest that BD may be associated with abnormalities in mitochondrial function. Here we critically review findings from brain imaging and from preclinical studies that investigated markers of energy metabolism in BD. Research with postmortem brain and peripheral tissue revealed changes in size and distribution of mitochondria, as well as decreased mitochondrial electron transport chain function, increased oxidative stress, and increased lipid and protein damage. PET imaging studies revealed decreased glucose metabolism in sub-areas of the prefrontal cortex, amygdala, and hippocampus structures in BD. On the other hand, increased lactate levels in BD have been found in cerebrospinal fluid and in gray matter by magnetic resonance spectroscopy, which suggest that distinct pathophysiological processes may be region-specific. Resting state fMRI studies have demonstrated decreased functional connectivity between fronto-limbic circuits. In conclusion, these results support the hypothesis of mitochondrial dysfunction in BD and suggest that BD is associated with decreased energy production and a shift towards anaerobic glycolysis. Such changes in energy metabolism can potentially decrease cell plasticity and ultimately disrupt brain circuits associated with mood and cognitive control.


El trastorno bipolar (TB) es una enfermedad mental crónica grave caracterizada por episodios de ánimo extremo, trastornos cognitivos y altas tasas de discapacidad. Varias líneas de evidencia sugieren que el TB puede estar asociado con anormalidades en la función mitocondrial. Aquí analizamos críticamente los hallazgos de las imágenes cerebrales y de los estudios preclínicos que han investigado los marcadores del metabolismo de energía en TB. Las investigaciones post mórtem basadas en tejidos cerebrales y tejidos periféricos revelaron cambios en el tamaño y en la distribución de las mitocondrias, además de una disminución en la funcionalidad de la cadena de transporte de electrones de las mitocondrias, un mayor estrés oxidativo y mayores daños lipídicos y proteínicos. Estudios con imágenes TEP revelan un metabolismo de glucosa disminuido en las subáreas de la corteza prefrontal, la amígdala y el hipocampo en TB. Por otro lado, se han hallado concentraciones mayores de lactato en TB en el líquido cefalorraquídeo cerebral y en la materia gris utilizando la espectroscopia con resonancia magnética, lo cual sugiere que los procesos fisiopatológicos individuales pueden ser específicos de las distintas regiones. Los estudios con resonancias magnéticas funcionales han demostrado una menor conectividad funcional entre los circuitos frontolímbicos. En conclusión, estos resultados apoyan la hipótesis de una disfunción mitocondrial en el TB y sugieren que el TB está asociado con una menor producción de energía y un cambio hacia la glicólisis anaeróbica. Estos cambios en el metabolismo energético pueden disminuir potencialmente la plasticidad celular y, en últimas, perturbar los circuitos cerebrales asociados con el estado de ánimo y el control cognitivo.

13.
J Surg Res ; 167(2): e307-13, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-19959187

RESUMO

BACKGROUND: Some of the postulated molecular mechanisms of sepsis progression are linked with the imbalance between reactive oxygen species (ROS) production and its degradation by cellular antioxidant pathways. Some studies have correlated plasma oxidative stress, inflammatory markers, and clinical markers of organ failure, but none performed this in a systematic way, determining in situ oxidative and inflammatory markers and correlating these with markers of organ failure. MATERIALS AND METHODS: Rats subjected to cecal ligation and puncture (CLP) were treated with basic support or antioxidants and killed 12 h after to determine thiobarbituric acid reactive species (as an index of oxidative damage), superoxide dismutase (SOD), catalase (CAT), and myeloperoxidase (MPO) (as an index of neutrophil infiltration) in the kidney and lung. In addition, protein content in bronchoalveolar lavage fluid (as an index of lung alveolo-capillary dysfunction) and plasma urea (as an index of kidney injury) were measured at the same time. RESULTS: In the CLP group, we found a positive correlation between thiobarbituric acid reactive species (TBARS) and markers of organ injury in lung and kidney. Oxidative damage is correlated with an increase in SOD/CAT ratio only in the lung. In contrast, oxidative damage is correlated with MPO activity in the kidney, but not lung, suggesting different sources of oxidative damage depending on the analyzed organ. These reflect differences on the effects of basic support and antioxidants on organ dysfunction after sepsis. CONCLUSION: Despite the general occurrence of oxidative damage in different organs during sepsis development and a positive correlation between oxidative markers and organ injury, antioxidant effects seemed to depend not only on the diminution of oxidative damage but also on its anti-inflammatory activity.


Assuntos
Antioxidantes/uso terapêutico , Catalase/metabolismo , Insuficiência de Múltiplos Órgãos/prevenção & controle , Infiltração de Neutrófilos/fisiologia , Estresse Oxidativo/fisiologia , Sepse/complicações , Superóxido Dismutase/metabolismo , Acetilcisteína/uso terapêutico , Animais , Desferroxamina/uso terapêutico , Modelos Animais de Doenças , Rim/metabolismo , Pulmão/metabolismo , Masculino , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/microbiologia , Peroxidase/metabolismo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ureia/sangue
14.
Cell Biol Toxicol ; 25(6): 545-60, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19043787

RESUMO

There is a growing body of evidence showing that vitamin A induces toxic effects in several experimental models and in human beings. In the present work, we have investigated the effects of short-term vitamin A supplementation on the adult rat liver redox status. We have found that vitamin A at therapeutic doses induces a hepatic oxidative insult. Furthermore, we have observed increased antioxidant enzyme activity in the liver of vitamin-A-treated rats. Additionally, some mitochondrial dysfunction was found since superoxide anion production was increased in vitamin-A-treated rat liver submitochondrial particles, which may be the result of impaired mitochondrial electron transfer chain activity, as assessed here. We have also isolated rat liver mitochondria and challenged it with 75 muM CaCl2, a non-oxidant agent that is able to induce mitochondrial oxidative stress indirectly. We have found that mitochondria isolated from vitamin-A-treated rat liver are more sensitive to CaCl2 than control mitochondria regarding the redox status. Importantly, vitamin A seems to alter mitochondrial redox status independently of the participation of the mitochondrial permeability transition pore, which is activated by Ca2+ ions since cyclosporin A did not prevent the oxidative insult elicited by Ca2+ addition. Overall, we show here that mitochondria are a target of vitamin-A-associated toxicity also in vivo.


Assuntos
Cálcio/metabolismo , Mitocôndrias Hepáticas , Oxirredutases/metabolismo , Vitamina A , Animais , Cálcio/farmacologia , Ciclosporina/farmacologia , Transporte de Elétrons , Metabolismo Energético/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Homeostase/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Partículas Submitocôndricas/metabolismo , Superóxidos/metabolismo , Vitamina A/administração & dosagem , Vitamina A/efeitos adversos
15.
Cell Biol Int ; 32(1): 100-6, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17942326

RESUMO

Even though retinoids are widely used as adjuvant in chemotherapeutic interventions to improve cancer cell death, their mechanism(s) of action involves multiple overlapping pathways that remain unclear. We have previously shown that vitamin A, the natural precursor of the retinoids, induces oxidative-dependent cytochrome c release from isolated mitochondria, suggesting a putative mechanism for apoptosis activation. Using Sertoli cells in culture, we show that retinol causes mitochondrial-dependent apoptosis, involving oxidative stress. Apoptosis was evaluated by nuclear morphology, DNA fragmentation, and caspase-3/7 activity. Retinol induced oxidant- and time-dependent imbalance of several mitochondrial parameters, cytochrome c release and caspase-3/7 activation, leading cells to commit apoptosis. All parameters tested were attenuated or blocked by trolox co-administration, suggesting that retinol induces apoptosis through oxidative damage, which mitochondria plays a pivotal role.


Assuntos
Apoptose/efeitos dos fármacos , Mitocôndrias/fisiologia , Vitamina A/farmacologia , Animais , Caspase 3/metabolismo , Caspase 7/metabolismo , Células Cultivadas , Citocromos c/metabolismo , Ativação Enzimática , Masculino , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Células de Sertoli/ultraestrutura
16.
Neurosci Lett ; 406(3): 281-4, 2006 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-16930840

RESUMO

Malnutrition affects a large number of children worldwide. Inadequate nutrition during pre- and postnatal period may alter brain development resulting in biochemical, physiological and anatomical changes which in turn could cause behavioral abnormalities. The impairment of the central nervous system following protein deficit have been extensively studied and this deprivation produces deleterious effects upon cerebral structures. The aim of this study was to identify oxidative parameters present in the developing brain as consequence of maternal protein malnutrition. Female Wistar rats were fed a normal protein diet (25% casein) or low protein diet (8% casein) from the time of conception up to 21 days after the parturition. In addition, the diets were supplemented or not with l-methionine. Cortex and cerebellum were removed from offspring to determine the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and the levels of lipoperoxidation (TBARS). Our findings demonstrated heterogeneity in response to protein restriction. The levels of lipoperoxidation were increased in the cerebellum of malnourished offspring. Methionine supplementation caused an increase in lipoperoxidation in both brain structures. CAT activity was decreased in the cerebellum of the offspring supplemented with methionine whereas the cerebellum of malnourished pups with or not methionine supplementation showed a decrease in SOD activity. The activity of SOD in the cortex did not differ among groups. CAT activity, however, was increased in the cortex of malnourished pups supplemented or not with methionine. Thus, these results provide clues to the knowledge of malnutrition effects upon the brain.


Assuntos
Catalase/metabolismo , Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Desnutrição/metabolismo , Desnutrição Proteico-Calórica/metabolismo , Superóxido Dismutase/metabolismo , Animais , Animais Recém-Nascidos , Biomarcadores , Cerebelo/crescimento & desenvolvimento , Córtex Cerebral/crescimento & desenvolvimento , Feminino , Peroxidação de Lipídeos/fisiologia , Masculino , Metionina/administração & dosagem , Gravidez , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
17.
Life Sci ; 77(19): 2398-411, 2005 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-15932762

RESUMO

Organoselenium compounds have a potential thiol peroxidase-like activity. Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organic selenium compounds. Using TRAP assay of chemiluminescense we have shown that diphenyl diselenide clearly possesses a pro-oxidant property. For an investigation on the mechanisms of this property, we used mutant strains of Saccharomyces cerevisiae defective in antioxidant defenses, i.e. in superoxide dismutase, in biosynthesis of glutathione, and the transcription factor yAP-1-lacking yap 1 mutant that cannot activate genes of the oxidative stress response. Exposure of growing cultures to the drug increased cell sensitivity to oxidizing agents. The pro-oxidant effect was independent of the metabolic condition or of the oxidative mutagen tested. N-acetylcysteine, a precursor of glutathione biosynthesis, could neutralize the pro-oxidant effects of diphenyl diselenide by stimulating an increase of endogenous glutathione biosynthesis or by directly binding to the drug. Vitamin E (Trolox), a known antioxidant, was also able to protect S. cerevisiae against the pro-oxidant effect of diphenyl diselenide. In vitro assays showed that diphenyl diselenide interacts non-enzymatically with the thiol group of glutathione.


Assuntos
Derivados de Benzeno/toxicidade , Compostos Organosselênicos/toxicidade , Oxidantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Derivados de Benzeno/antagonistas & inibidores , Bleomicina/farmacologia , Dano ao DNA/efeitos dos fármacos , Fermentação , Depuradores de Radicais Livres/farmacologia , Genes Fúngicos/genética , Glutationa/metabolismo , Medições Luminescentes , Luminol/química , Mutação/fisiologia , Compostos Organosselênicos/antagonistas & inibidores , Oxigênio/metabolismo , Saccharomyces cerevisiae/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Vitamina E/farmacologia
18.
Environ Mol Mutagen ; 41(5): 360-9, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12802807

RESUMO

Fresh and processed cashew (Anacardium occidentale) apple juice (CAJ) are among the most popular drinks in Brazil. Besides their nutritional benefits, these juices have antibacterial and antitumor potential. The chemical constituents of both the fresh juice and the processed juice (cajuina) were analyzed and characterized as complex mixtures containing high concentrations of vitamin C, various carotenoids, phenolic compounds, and metals. In the present study, these beverages exhibited direct and rat liver S9-mediated mutagenicity in the Salmonella/microsome assay with strains TA97a, TA98, and TA100, which detect frameshifts and base pair substitution. No mutagenicity was observed with strain TA102, which detects oxidative and alkylating mutagens and active forms of oxygen. Both CAJ and cajuina showed antioxidant activity as determined by a total radical-trapping potential assay. To test whether this antioxidant potential might result in antimutagenesis, we used a variation of the Salmonella/microsome assay that included pre-, co-, and posttreatment of hydrogen peroxide-exposed Salmonella typhimurium strain TA102 with the juices. CAJ and cajuina protected strain TA102 against mutation by oxidative damage in co- and posttreatments. The antimutagenic effects during cotreatment with hydrogen peroxide may be due to scavenging free radicals and complexing extracellular mutagenic compounds. The protective effects in posttreatment may be due to stimulation of repair and/or reversion of DNA damage. The results indicate that CAJ and cajuina have mutagenic, radical-trapping, antimutagenic, and comutagenic activity and that these properties can be related to the chemical constituents of the juices.


Assuntos
Anacardium/química , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Bebidas , Peróxido de Hidrogênio/toxicidade , Animais , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Testes de Mutagenicidade , Ratos , Ratos Sprague-Dawley , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA