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Recherche de nouveaux chélateurs du manganèse en vue de la détoxication de l'organisme : Études in vivo et in vitro chez le rat

Abstract : This study dealt with new manganese chelating agents. The first part is devoted to the development of a subchronic intoxication protocol. Rats were intoxicated by intraperitoneal injections, the oral route being not sufficiently effective since less than 2%of the ingested manganese are absorbed. This result suggests that the risks of intoxication by diet are very weak even null. Accumulation of manganese was observed in well-known target issues (spleen, central nervous system, bones, erythrocytes), but also in bone marrow. In our experimental conditions, the presence of manganese in the brain induced no neurochemical or histological modifications. The second part of this work concerns the in vivo study of new chelating agents selected beforehand for their in vitro effectiveness to complex with manganese. The most effective compounds in vitro (polyaminopolycarboxylic acids) caused only a partial detoxification of the organism; they remained without effect on manganese bound to the erythrocytes (haemoglobin). This results led us to the following assumptions : manganese (Mn2+), which chemical properties are close to those of iron (Fe2+), would take the place of this last not only in haemoglobin, that is already known, but also in the cytochromes of the respiratory chain. So, based on the standard redox potentials of the cytochromes containing manganese, it was possible to show the inability of these structures to reduce oxygen. This incomplete oxygen reduction would lead to the formation of free radicals which are capable of accelerating cells aging and oxidizing dopamine in benzoquinones, implied in the neurological symptoms observed in chronic manganism
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Pascale Missy. Recherche de nouveaux chélateurs du manganèse en vue de la détoxication de l'organisme : Études in vivo et in vitro chez le rat. Toxicologie. Université Paul Verlaine - Metz, 2001. Français. ⟨NNT : 2001METZ023S⟩. ⟨tel-01775443⟩



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