Guliaev A E, Kivman G Ia
Antibiot Med Biotekhnol. 1985 Jan;30(1):50-4.
Interaction of gentamicin and sisomicin with isolated subcellular fractions of the rat liver and the kidney cortical layer was studied. Distribution of the antibiotics was investigated in a system with the volume ratio of the main components (organoids and cytosol-dissolved drug) simulating the natural volume ratio of the cytoplasm and organoids in the cells. It was shown that lysosomes were the most active elements in binding antibiotics. The microsomes and mitochondria were less active. By the binding capacity the subcellular structures of the kidneys were superior to the analogous structures of the liver. Dissociation of the organoid complexes with the antibiotics was possible, the mobility of the sisomicin complexes being higher than that of the gentamicin complexes. During intracellular distribution the major amount of every of the above aminoglycosides was absorbed by the organoids. Up to 20 per cent of gentamicin and up to 30 per cent of sisomicin remained in the cytoplasm in the active form. The characteristic features of the intracellular distribution of sisomicin (build up of high levels of the free antibiotic in the cytoplasm and relatively easy dissociation of the antibiotic complexes with the organoids of the kidney cortical layer) may define the higher activity of sisomicin as compared to that of gentamicin against intracellularly located microorganisms and its lower potential nephrotoxicity.
研究了庆大霉素和西索米星与大鼠肝脏和肾皮质层分离的亚细胞组分的相互作用。在一个系统中研究了抗生素的分布,该系统中主要成分(细胞器和胞质溶胶溶解的药物)的体积比模拟了细胞中细胞质和细胞器的自然体积比。结果表明,溶酶体是结合抗生素最活跃的成分。微粒体和线粒体的活性较低。肾脏的亚细胞结构在结合能力上优于肝脏的类似结构。细胞器与抗生素的复合物可以解离,西索米星复合物的迁移率高于庆大霉素复合物。在细胞内分布过程中,上述每种氨基糖苷类药物的主要部分被细胞器吸收。高达20%的庆大霉素和高达30%的西索米星以活性形式留在细胞质中。西索米星在细胞内分布的特征(细胞质中游离抗生素水平的积累以及抗生素与肾皮质层细胞器复合物相对容易解离)可能决定了西索米星与庆大霉素相比,对细胞内定位的微生物具有更高的活性,以及更低的潜在肾毒性。