Dissertação

Avaliação do efeito protetor da prolactina em linfócitos expostos a ação do metilmercúrio

Mercury can be found in several forms, as being organic methylmercury (MeHg), considered the most toxic. Readily absorbed orally, accumulates in the food chain and is amplified in aquatic carnivores, especially in fish, hence the greater risk to populations that preferentially feed on them, such as...

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Autor principal: JESUS, Maria Izabel de
Grau: Dissertação
Idioma: por
Publicado em: Universidade Federal do Pará 2013
Assuntos:
Acesso em linha: http://repositorio.ufpa.br/jspui/handle/2011/4501
Resumo:
Mercury can be found in several forms, as being organic methylmercury (MeHg), considered the most toxic. Readily absorbed orally, accumulates in the food chain and is amplified in aquatic carnivores, especially in fish, hence the greater risk to populations that preferentially feed on them, such as riparian Amazonian populations. The neurotoxic effect of this form of mercury has been widely demonstrated by epidemiological and experimental studies. Some of these studies have also shown that hormones and antioxidants may act by protecting the body against the deleterious effects of mercury. Prolactin is a hormone that has such protective action, but also acts as a proinflammatory cytokine. Since MeHg can also act as an immunotoxic substance, we have studied the cytoprotective action of PRL in continuous cultures of strain B95-A primate lymphocytes in order to assess their vulnerability to MeHg and its responsiveness to the action of PRL. In order to assess the functional integrity of lymphocytes exposed to MeHg we used to test color reaction for 3 - (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT), which detects activity mitochondrial metabolism. To evaluate the immune response of lymphocytes, measures of tumor necrosis factor alpha (TNF α) concentration in the middle were performed by ELISA. It is a proinflammatory cytokine released in response to cellular injury from different causes, including oxidative stress, one of the most obvious acute effects of MeHg, and this cytokine also be able to answer prolactin regulation in human lymphocytes. After 18 hours of cultivation exposure to increasing concentrations of the metal (0.1, 1, 5, 10 and 50 mM) showed significant decrease in dose-dependent cell viability from 1 mM (35%) and progressively up to 50 mM (80%), when few intact cells were found in the cultivation. A biphasic effect in a "bell" shaped occurred in the release of TNF-α, where lower concentrations of MeHg inhibited (0.1 and 1 mM) stimulated the intermediate (5 mM) and the two largest (10 and 50 mM) returned to inhibit. Prolactin also decreased the cell viability by about 30% only at the highest dose (10 nM).Moreover, at a dose of 1 nM prevented PRL 40% decrease in cell viability due to exposure to 5 mM MeHg. This dose of 1 nM PRL was the only one to stimulate the release of TNF-α, but curiously reversed the release of this cytokine when combined with 5 mM of MeHg, concentrations that also stimulated the secretion of TNF-α. The results confirmed the toxicity of MeHg to lymphocytes of primates (strain B95-A) and its reversion by possible protective action of PRL. A biphasic effect on the secretion of TNF α resulted from MeHg exposure, suggesting the presence of different mechanisms of cytotoxic action resulting from mercury. Moreover, PRL was less effective in stimulating the secretion of that cytokine, reversing this response when the associated with MeHg. However, these results are preliminary and require a more accurater study for their complete elucidation.