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L'acide ascorbique réduit les dommages génétiques causés par la miltéfosine (hexadécylphosphocholine) chez les animaux infectés par Leishmania (Leishamnia) infantum sans diminuer son activité antileishmaniale.

La leishamaniose est une maladie négligée causée par plus de 20 espèces de Leishmania et présente dans plus de cent pays. La miltefosine (hexadécylphosphocholine) est le seul médicament oral utilisé dans le traitement des leshmanioses, y compris dans les cas d’infections résistant à l’antimoine pentavalent. Notre groupe a récemment démontré la capacité de la miltéfosine à provoquer des lésions génomiques par oxydation de l'ADN. Reconnaissant que les composés antioxydants peuvent potentiellement moduler les espèces réactives de l'oxygène (ROS), notre étude a vérifié si l'acide ascorbique réduisait les effets génotoxiques et mutagènes causés par la miltéfosine et nuisait à l'efficacité du médicament. À cette fin, des souris suisses non infectées ont reçu simultanément de la miltéfosine et de l'acide ascorbique (gavage et intrapéritonéal) simultanément (traitement à dose unique), en plus des traitements préalables et postérieurs (acide ascorbique 24 heures avant et après l'administration du médicament); de plus, les souris Balb / c infectées par Leishmania infantum ont reçu de la miltéfosine plus de l'acide ascorbique (traitement à doses répétées). Nous avons effectué des dosages de comètes, des tests de micronoyaux, des dosages de l'enzyme superoxyde dismutase et une charge parasitaire par le test de dilution limite. Nous avons observé que l’acide ascorbique administré par voie intrapéritonéale présentait un effet protecteur sur les dommages causés par la miltéfosine. Cependant, cet effet n'a pas été observé lorsque les mêmes doses ont été administrées par gavage, probablement en raison des faibles taux sériques de cet antioxydant. L'effet protecteur de l'acide ascorbique renforce le fait que la miltéfosine endommage l'ADN en oxydant ses bases azotées, qui sont réduites par l'acide ascorbique en raison de sa capacité à protéger le matériel génétique de l'action des ROS. Par conséquent, nos résultats montrent que ce médicament est efficace pour réduire la charge parasitaire de L. infantum.


Source: https://www.ncbi.nlm.nih.gov/pubmed/30578864


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