[泛酸衍生物,辅酶A生物合成前体,关于卡那霉素的抗毒性]。

Antibiotiki Pub Date : 1984-11-01
A G Moĭseenok, B F Dorofeev, V M Sheĭbak, T I Khomich
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引用次数: 0

摘要

研究了泛酸钙(CPN) b4′-磷酸-CPN (PCP)、泛酸钙(PT)和s -硫泛酸钙(SPN)对硫酸卡那霉素对白化小鼠急性毒性的影响。除PT外,上述泛酸衍生物均降低了抗生素毒性。SPN和PCP的抗毒系数(LD50/ED50)是CPN的1.3 ~ 1.4倍。卡那霉素(LD50的1/5)与CPN、PCP或PT (30 mg/kg bw相当于CPN)联合使用15 d,可抑制肝脏和脑内CoA总含量和参与n -乙酰化反应的游离CoA及其生物合成前体含量的增加。在整个实验过程中,这些物质的含量都在正常范围内。同时使用PCP和PT消除了由于使用卡那霉素引起的肝细胞质中泛酸激酶活性的一定增加。含维生素化合物PCP和SPN被推荐用于临床试验,作为预防卡那霉素治疗并发症的药物。
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[Antitoxic properties of pantothenic acid derivatives, precursors of coenzyme A biosynthesis, with regard to kanamycin].

The effect of calcium pantothenate (CPN)B 4'-phospho-CPN (PCP), pantetheine (PT) and calcium S-sulfopantetheine (SPN) on acute toxicity of kanamycin sulfate was studied on albino mice. The above derivatives of pantothenic acid except PT lowered the antibiotic toxicity. The coefficient of the antitoxic effect (LD50/ED50) of SPN and PCP was 1.3-1.4 times higher than that of CPN. The combined use of kanamycin (1/5 of the LD50) with CPN, PCP or PT (30 mg/kg bw was equivalent to CPN) for 15 days prevented the increase in the total content of CoA and in the content of the fraction of free CoA and the precursors of its biosynthesis participating in the reaction of N-acetylation in the liver and brain. The contents of these substances were within the normal during the whole experiment. A certain increase in the activity of pantothenate kinase in the liver cytosol due to the use of kanamycin was eliminated by the simultaneous use of PCP and PT. The vitamin-containing compounds PCP and SPN were recommended for the clinical trials as agents preventing complications of kanamycin therapy.

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