柔红霉素、阿霉素及其dna复合物在大鼠心室的积累、代谢和亚细胞定位

J.C. Blanchard , Y.-J. Schneider , R. Baurain, A. Trouet
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引用次数: 15

摘要

研究了柔红霉素(DNR)、多柔红霉素(DOX)及其DNA复合物在大鼠心脏心室的积累、代谢物的存在和亚细胞定位。静脉灌注游离DNR或DOX后,在心脏中回收等量的药物,而注射其DNA复合物后,积累水平为游离药物达到的42% (DNR)和32% (DOX)。给药DNR或DNR- dna后检测到柔红霉素和柔霉素酮,但DOX和DOX- dna仅检测到微量代谢物。以游离或DNA复合物形式注射的DNR的亚细胞分布相似。异速离心和差速离心表明,DNR可能与核DNA有关,与溶酶体的关系较小。相比之下,在注射游离DOX或络合DOX后,药物几乎完全与核DNA相关。讨论了这些药物在心脏蓄积的机制及其与心脏毒性的关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Accumulation, metabolism and subcellular localization of daunorubicin, doxorubicin and their DNA-complexes in rat heart ventricles

The accumulation in rat heart ventricles, the presence of metabolites and the subcellular localization of daunorubicin (DNR), doxorubicin (DOX) and their DNA complexes were investigated. After intravenous perfusion of free DNR or DOX, equal amounts of the drugs are recovered in the heart, whereas after injection of their DNA complexes, the accumulation levels represent 42% (DNR) and 32% (DOX) of those reached with the free drugs. Daunorubicinol and daunomycinone are detected after administration of DNR or DNR-DNA but only trace amounts of metabolites are found with DOX and DOX-DNA. Subcellular distributions of DNR injected as free or DNA complex are similar. Isopycnic and differential centrifugations indicate that DNR could be associated with nuclear DNA and to a smaller extent with lysosomes. By contrast, after injection of free or complexed DOX the drug is almost exclusively associated with the nuclear DNA. The mechanisms by which these drugs are accumulated by the heart and the relation with their cardiotoxicities are discussed.

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