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R. Iie-noiryeaiix, C. Manganesd, E. Viie-de, L. Detoxication-de-l-'organisme:, . Etudes et al.,

. La-première-partie-est-oonsacrée-À-la-nise-au-point-d-'un-protocole-d-'intoxicaton-subchronique, La voie intraperitoneale a été rete,nue pour imoxiquer les ratq la voie orale n'éhnt pas sufrsamment efficace, puisque moins de 2 To da mengmèsiç ingéré sont absorbés

, une accumulation de manganèse a été mise en évidence rtans des tssus cibles dejà connus (rate, système nerverD( central, os, globules rouges), mais également dans la moelle osseuse. Dans nos conditions d'intoximtion

, l'étude in vivo de noweaux chélateurs préalablement aelectionnés, pour leur bon powoir complexant vis-à-vis du mânganèse, par lme technique in vitro. Les composes les plus efficaces in vitro (acides polyaminopolycarboryliques) n'ont prwoqué qu'une détoxication partielle de I'organisme ; ils sont restés sans efret sur le mangarrèse fixé dans les globutes rouges (hémoglobine)

, aux propriétes chimiques voisines de celles du fer (Fe), se fixerait à la place de ce dernier non seuleme,rrt dans I'hémoglobine, ce qui est déjà oonnu' mais également dans les cytochromes de la chalne respiraeoire. De ce fait, en se basant sur les potentiels redox standard des cytochromes contqlânt dll menganèse, il a été possible de monter I'incapacité de ces structures à reduire I'o4ygène. Cette réduction incomplète de I'orygène conduirait à la formation de radicaux lihres, Ces résultats nous ont conduit arx hlpothèses suivantes

, Mots clés: marg:rnèse, intoxication, absorptim, chaîne chélaeeurs. radicanx orygénés, neurotoxicité, NEW MANGANESE CMLATING AGENTS FOR THE ORGANISM DETO)flFICATIONZ IN VIVO AND 'iV WTRO STTIDIES IN THE RAT Ihis study dealt with new mângânese chelating ag?Nrts

, rhe first part is d?voted to the dwelopment of a subchronic intoxicdion protocol. Rats were inoxicated by intraperitoneal injec'tions, the oral route being not srfrcient$ efrective, since less then 2 % of the ingested mângânese are absolbed. This result suggests that the risks of inoxication by diet are very weak even null

, Acqrmulaton ef menganese was observed in well-known target tissues (sple?N\ central nervous system, bones, rythrocytes), but dso in bone marrcw, our experimenlal conditions, the presence 6rf mengrncse in the brain urduced no neurochemical or hiSological modifications

, Ihe second part of this work concerns tlle in vivo sudy of new chelating ag?nts selected beforehand for their tn itro etrectiveness to complex with mlngânese. The most effective compounds in vitro Bolyaninorpolycarborylic acids) caused only a partiat detoxification of thc organism; they remained without

, whidr cbemical properties are cbro n 'hose of iron GÔ, would take the place of this last not only in ha?moglobitr, that is already knou4 but C$ in fre cytochromes of the reqpiratory chain. So, based on the standard rodox potentials of the qrtoclnocs nntaining nrtngnncre' it was possible to shoril the inability of thesc strtrctur?s to reôrce orygen Tlrir ncomplete o:ryg?Nl t?duction would lead to thc formation of froe radicals which are capable of aocelerating ocûr tging and sxi, Ihese rezults led us to the following assrrytions: mengnn?sc (À{n2)