RESUMO
Breastfeeding provides ideal nutrition and passive immunization for growing infants, protecting them from potentially fatal infectious diseases. Exclusive breastfeeding is recommended for at least six months and should be continued complementarity for another year. One of the justifications for this recommended practice is the prevention of allergic diseases, which has been controversial for many years. Here we reviewed data regarding breastfeeding practices and hypothesized that exclusive breastfeeding for long periods may affect the availability of helper T lymphocyte 1-polarizing antigens in babies. This fact could favor helper T lymphocyte 2 (TH2) phenotype development and consequently increase the incidences of allergies, although we have found no consistent evidence in the literature supporting or denying that breastfeeding plays a role in allergic diseases. The literature mostly presents inconsistencies and/or methodological issues precluding a final answer to this issue. The development of the adaptive immune system depends on exposure to antigens that elicit the production of specific cytokines and activates T lymphocyte populations. It is believed that a promotion of the TH2 phenotype to the detriment of another lymphocyte subset takes place, although the exact knowledge about when this process begins is still under investigation. Therefore, the recent increase in allergy incidence might be partly explained by breastfeeding practices in the world and by the hypothesis presented here, affecting the baby's immune system development through selective antigen availability.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Hipersensibilidade/imunologia , Subpopulações de Linfócitos T/imunologia , Aleitamento Materno , Citocinas/metabolismo , Humanos , Hipersensibilidade/epidemiologia , Imunidade Materno-Adquirida , Modelos ImunológicosRESUMO
Schistosomiasis is a parasitic disease caused by trematode worms from the Schistosoma genus and is characterized by high rates of morbidity. The main organs affected in this pathology, such as liver, kidneys and spleen, are shifted to a pro-oxidant state in the course of the infection. Here, we compared oxidative stress parameters of liver, kidney and spleen with other organs affected by schistosomiasis - heart, brain cortex and lungs. The results demonstrated that mice infected with Schistosoma mansoni had altered non-enzymatic antioxidant status in lungs and brain, increased carbonyl levels in lungs, and a moderate level of oxidative stress in heart. A severe redox imbalance in liver and kidneys and decreased non-enzymatic antioxidant capacity in spleen were also observed. Superoxide dismutase and catalase activities were differently modulated in liver, kidney and heart, and we found that differences in Superoxide dismutase 2 and catalase protein content may be responsible for these differences. Lungs had decreased receptor for advanced glycation endproduct expression and the brain cortex presented altered tau expression and phosphorylation levels, suggesting important molecular changes in these tissues, as homeostasis of these proteins is widely associated with the normal function of their respective organs. We believe that these results demonstrate for the first time that changes in the redox profile and expression of tissue-specific proteins of organs such as heart, lungs and brain are observed in early stages of S. mansoni infection.
Assuntos
Estresse Oxidativo/imunologia , Receptores Imunológicos/metabolismo , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/imunologia , Proteínas tau/metabolismo , Animais , Catalase/metabolismo , Córtex Cerebral/parasitologia , Córtex Cerebral/patologia , Regulação da Expressão Gênica/fisiologia , Pulmão/parasitologia , Pulmão/patologia , Camundongos , Miocárdio/patologia , Oxirredução , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/genética , Esquistossomose mansoni/metabolismo , Esquistossomose mansoni/parasitologia , Superóxido Dismutase , Proteínas tau/genéticaRESUMO
Vitamin A (retinol) is widely used as an antioxidant in therapeutic interventions and dietary supplementations. However, the redox properties of retinoids have been the subject of intense debate in the last few years, as recent works observed deleterious effects caused by retinol supplementation in clinical trials. In the present work, we show that retinol treatment (7 microM, 24 h) led to catalase (EC 1.11.1.6; CAT) activation in cultured Sertoli cells by increasing its protein content in a reactive species-dependent manner. Retinol treatment also increased cell lipoperoxidation, assessed by determination of thiobarbituric acid-reactive substances (TBARS), and intracellular reactive species production, determined by the real-time dihydrochlorofluorescein (DCFH-DA) assay. However, no alterations on CAT mRNA expression (assessed by RT-PCR) were observed, indicating an effect independent of CAT gene-transcription regulation. Importantly, all the effects induced by retinol were inhibited by the antioxidant Trolox, a hydrophilic analogue of alpha-tocopherol. These results show for the first time that retinol increases CAT activity by a redox-dependent modulation of its protein content in a cell culture model. CAT activity or expression are widely used as indexes of oxidative stress in biological systems; since no changes in CAT mRNA expression were detected in these conditions, the use of CAT gene-transcription activation when assessing oxidative stress should be re-evaluated.
Assuntos
Catalase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/enzimologia , Vitamina A/farmacologia , Animais , Catalase/genética , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Células de Sertoli/citologiaRESUMO
In early reports our research group has demonstrated that 7 microM retinol (vitamin A) treatment leads to many changes in Sertoli cell metabolism, such as up-regulation of antioxidant enzyme activities, increase in damage to biomolecules, abnormal cellular division, pre-neoplasic transformation, and cytoskeleton conformational changes. These effects were observed to be dependent on the production of reactive oxygen species (ROS), suggesting extra-nuclear (non-genomic) effects of retinol metabolism. Besides 7 microM retinol treatment causing oxidative stress, we have demonstrated that changes observed in cytoskeleton of Sertoli cells under these conditions were protective, and seem to be an adaptive phenomenon against a pro-oxidant environment resulting from retinol treatment. We have hypothesized that the cytoskeleton can conduct electrons through actin microfilaments, which would be a natural process necessary for cell homeostasis. In the present study we demonstrate results correlating retinol metabolism, actin architecture, mitochondria physiology and ROS, in order to demonstrate that the electron conduction through actin microfilaments might explain our results. We believe that electrons produced by retinol metabolism are dislocated through actin microfilaments to mitochondria, and are transferred to electron transport chain to produce water. When mitochondria capacity to receive electrons is overloaded, superoxide radical production is increased and the oxidative stress process starts. Our results suggested that actin cytoskeleton is essential to oxidative stress production induced by retinol treatment, and electrons conduction through actin microfilaments can be the key of this correlation.
Assuntos
Actinas/metabolismo , Elétrons , Estresse Oxidativo , Células de Sertoli , Vitamina A/farmacologia , Actinas/ultraestrutura , Animais , Citocalasina B/metabolismo , Citoesqueleto/metabolismo , Citoesqueleto/ultraestrutura , Masculino , Potenciais da Membrana/fisiologia , Mitocôndrias/metabolismo , Fosforilação , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Vitaminas/farmacologiaRESUMO
Follicle-stimulating hormone (FSH) and vitamin A (retinol) are two of the main regulators of the male reproductive system. Recently, it has been described that extracellular purines can affect some important reproductive-related functions in Sertoli cells and germinative cells, by activating specific purinergic receptors. In this work, we report that both FSH and retinol are able to induce changes in the levels of extracellular purines of cultured rat Sertoli cells. FSH induced an increase in adenosine, mainly caused by enhanced ecto-ATPase activity, while retinol increased xanthine and hypoxanthine levels, and decreased uric acid concentration by an unknown mechanism. These data indicate that purinergic signaling may be involved in the control and/or regulation of some of the reproductive-related actions of these hormones.
Assuntos
Hormônio Foliculoestimulante/farmacologia , Purinas/metabolismo , Células de Sertoli/efeitos dos fármacos , Vitamina A/farmacologia , Animais , Hormônio Foliculoestimulante/metabolismo , Cinética , Masculino , Ratos , Células de Sertoli/metabolismo , Fatores de Tempo , Vitamina A/metabolismoRESUMO
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 , Sequestradores 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/farmacologiaRESUMO
Retinol (vitamin A) is involved in several cellular processes, like cell division, differentiation, transformation and apoptosis. Although it has been shown that retinol is a limitant factor for all these processes, the precise mechanisms by which retinol acts are still unknown. In the present study we hypothesised that alterations in the cytoskeleton of Sertoli cells induced by retinol supplementation could indicate an adaptive maintenance of its functions, since it plays an important role in the transformation process that we observed. Previous results demonstrated that Sertoli cells treated with retinol showed an oxidative imbalance, that leads the cell to two phenotypes: apoptosis or transformation. Our group has identified characteristics of Sertoli cells transformed by retinol which results in normal cell functions modification. In the present study the actin filament fluorescence assay and the deformation coefficient showed a modification in the morphology induced by retinol. We also observed an oxidative alteration in isolated cytoskeleton proteins and did not show alterations when these proteins are analyzed by electrophoreses. Our results showed an increase in mitochondria superoxide production and a decrease in nitric oxide levels. All results were partially or completely reverted by co-treatment of the antioxidant Trolox. These findings suggest that the cytoskeleton components suffer individual alterations in different levels and that these alterations generate a global phenotype modification and that these processes are probably ROS dependent. We believe that the results from this study indicate an adaptation of the cytoskeleton to oxidative imbalance since there was not a loss of its function.
Assuntos
Citoesqueleto/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células de Sertoli/metabolismo , Vitamina A/farmacologia , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Actinas/efeitos dos fármacos , Actinas/metabolismo , Animais , Células Cultivadas , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/efeitos dos fármacos , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Masculino , Estresse Oxidativo , Fenótipo , Ratos , Ratos Wistar , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/patologia , Superóxidos/metabolismoRESUMO
In spite of being one of the first vitamins to be discovered, the full range of biological activities of Vitamin A remains incomplete. A growing body of evidence has demonstrated an apparent enhancement of carcinogenesis, induced by dietary retinol. Since DNA damage is a well-recognized inducer of carcinogenesis, the aim of this study was to test the possible genotoxic effect of dietary retinol, using different types of bioassays. Retinol caused an increased recombinogenic activity in Drosophila melanogaster larvae as measured by the SMART test. In mammalian cell cultures, retinol supplementation-induced DNA double-strands breaks (DSB) and single-strands breaks (SSB), cell cycle progression and proliferative focus formation in terminal-differentiated rat Sertoli cells and increased DNA fragmentation in Chinese hamster lung fibroblasts (V79 cells), as measured by the comet assay. Altogether, our results suggest that retinol causes DNA damage and chromosomal rearrangements, which may disturbs key physiological processes and lead to cell cycle progression and preneoplasic transformation of terminal-differentiated mammalian cells.