Expressão de adrenoceptores beta em tecido cardíaco de ratos intoxicados por cádmio e tratados com concentrado de suco de uva
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2013-05-29
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Dissertação de mestrado
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Os metais pesados são os agentes tóxicos mais conhecidos do homem. O cádmio é um metal pesado tóxico amplamente encontrado em lugares expostos a contaminação por poluentes industriais e locais de operação de resíduos. Tende a poluir o solo agrícola e o mar, afetando a dieta humana, tornando-a fonte primária de exposição ao homem entre os não fumantes. O cádmio afeta principalmente os rins, o fígado e os ossos, e pode ter relação com prognóstico de mortalidade por câncer. Entretanto, carecem estudos que investiguem seus efeitos sobre o coração. Alguns estudos sugerem que o cádmio pode causar aterosclerose e promover a geração de espécies reativas de oxigênio, além de reduzir a intrínseca capacidade tecidual de neutralizá-las. A intoxicação pelo cádmio é de difícil tratamento. A utilização de substâncias com capacidade antioxidante constitui uma alternativa terapêutica ao uso de agentes quelantes. Nesta classe, um dos agentes mais promissores são os polifenóis, presentes em uvas e bebidas derivadas. Os objetivos principais deste trabalho foram caracterizar a população de adrenoceptores cardíacos beta 1 e 2 pela técnica de western blot em ratos wistar adultos intoxicados com CdCl2 em dose única,intraperitoneal,(1,2 mg/Kg de peso corporal)e tratados por 60 dias com concentrado suco de uva (2,36 g/Kg/dia), rico em polifenóis, secundariamente foram avaliadas alterações de consumo de ração, massa corporal, massa relativa do coração e suas câmaras e massa das glândulas supra renais. A intoxicação por cádmio na dose administrada neste estudo, com ou sem o tratamento com o concentrado suco de uva não promoveu alterações sobre o ganho de massa corporal e sobre a massa cardíaca. Entretanto a intoxicação por cádmio causou alterações na massa das glândulas adrenais e na proporção dos subtipos de adrenoceptores β em tecido cardíaco uma vez que houve down-regulation de adrenoceptores β1 e up-regulation de adrenoceptores β2. O tratamento com concentrado de suco de uva foi efetivo tanto em atenuar o aumento da massa adrenal do grupo tratado como o aumento da expressão do adrenoceptor β2 induzido pelo cádmio mas não modificou seu efeito sobre a expressão dos adrenoceptores β1. Não é possível esclarecer a partir dos dados obtidos até o momento se estas alterações são adaptativas ou deletérias ao coração porém o estudo de tais modificações pode auxiliar na compreensão das alterações cardíacas observadas na espécie humana após exposição ao cádmio.
Cadmium is a heavy metal found in cigarettes. It also contaminates the food, being the primary source of exposure and intoxication among nonsmokers. Poisoning by cadmium is treated with chelating agents, but the use of antioxidants is an alternative therapy. Cadmium mainly effects the kidneys, liver and bones, and may be related to the prognosis of mortality by cancer. However, its effects on the heart remain unclear. The objective of this study was to investigate the possible occurrence of changes in the expression of β1 and β2 subtypes of cardiac adrenoceptors in male adult Wistar rats intoxicated with CdCl2 and whether the ingestion of concentrated grape juice can change this picture. Animals were assigned to one of the following groups: control; intoxicated with a single dose of CdCl2 (1.2 mg/Kg, ip); treated for 60 days with daily doses (2.36 g/kg) of concentrated grape juice (G8000 ®, containing 4.5% of resveratrol); intoxicated with CdCl2 and concomitantly treated with concentrated grape juice. The results showed no significant difference between groups with respect to body mass gain during the treatment period or heart mass. The expression of β1-adrenoceptors was lower in the heart of rats intoxicated with CdCl2, treated or not with concentrated grape juice. The treatment with the concentrated grape juice did not significantly alter this effect. Cadmiun also induced an increase in the expression of cardiac β2-adrenoceptors, which was reduced in the rats treated with concentrated grape juice at rates lower than those observed in the control group. The concentrated grape juice alone did not cause changes in the expression of this receptor in the control group. It is concluded that the cadmium poisoning caused changes in the proportion of β-adrenoceptor subtypes in cardiac tissue, since there was down-regulation of β1-adrenoceptors and up-regulation of β2-adrenoceptors. Treatment with concentrated grape juice was effective attenuating the increased expression of the β2-adrenoceptors induced by cadmium but did not modify its effect on the expression of β1-adrenoceptors.
Cadmium is a heavy metal found in cigarettes. It also contaminates the food, being the primary source of exposure and intoxication among nonsmokers. Poisoning by cadmium is treated with chelating agents, but the use of antioxidants is an alternative therapy. Cadmium mainly effects the kidneys, liver and bones, and may be related to the prognosis of mortality by cancer. However, its effects on the heart remain unclear. The objective of this study was to investigate the possible occurrence of changes in the expression of β1 and β2 subtypes of cardiac adrenoceptors in male adult Wistar rats intoxicated with CdCl2 and whether the ingestion of concentrated grape juice can change this picture. Animals were assigned to one of the following groups: control; intoxicated with a single dose of CdCl2 (1.2 mg/Kg, ip); treated for 60 days with daily doses (2.36 g/kg) of concentrated grape juice (G8000 ®, containing 4.5% of resveratrol); intoxicated with CdCl2 and concomitantly treated with concentrated grape juice. The results showed no significant difference between groups with respect to body mass gain during the treatment period or heart mass. The expression of β1-adrenoceptors was lower in the heart of rats intoxicated with CdCl2, treated or not with concentrated grape juice. The treatment with the concentrated grape juice did not significantly alter this effect. Cadmiun also induced an increase in the expression of cardiac β2-adrenoceptors, which was reduced in the rats treated with concentrated grape juice at rates lower than those observed in the control group. The concentrated grape juice alone did not cause changes in the expression of this receptor in the control group. It is concluded that the cadmium poisoning caused changes in the proportion of β-adrenoceptor subtypes in cardiac tissue, since there was down-regulation of β1-adrenoceptors and up-regulation of β2-adrenoceptors. Treatment with concentrated grape juice was effective attenuating the increased expression of the β2-adrenoceptors induced by cadmium but did not modify its effect on the expression of β1-adrenoceptors.
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Citação
VIEIRA, Daniel Malingre. Expressão de adrenoceptores beta em tecido cardíaco de ratos intoxicados por cádmio e tratados com concentrado de suco de uva. 2013. 85f. Dissertação (Mestrado) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2013.