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THE PROTECTIVE ROLE OF ZINC AND N-ACETYLCYSTEINE IN MODULATING ZIDOVUDINE INDUCED HEMATOPOIETIC TOXICITY

机译:锌和N-乙酰半胱氨酸在调节齐多夫定引起的血细胞毒性中的保护作用

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The role of zinc and N-acetylcysteine (NAC) has been investigated in protecting the hematopoietic progenitor cells from zidovudine (AZT)-induced toxicity. Murine bone marrow progenitor cells (BMPC, 1 x 10(6)) were exposed to various concentrations (0.1-50 mu M) of AZT in the presence and absence of zinc acetate (100 mu M) or NAC (100 mu M). The cell survival was determined by the colony forming assays of erythroid (CFU-E) and granulocytic (CEU-GM) lineage. The IC50 values of AZT in the presence of zinc were increased approximately 3-fold (from 3.0 to 9.5 mu M) in the CFU-E assay and 7-fold (from 4.3 to 28.8 mu M) in the CFU-GM assay whereas in the presence of NAC, the IC50 values were increased by 2- and 4-fold, respectively. To delineate the mechanism of significant protection of BMPC by zinc, the mRNA levels of metallothionein (MT) were monitored by using a 31-mer cDNA probe. Zinc produced a concentration-dependent increase in the MT mRNA levels in BMPC. These results suggest that zinc and NAC dietary supplementation can be conveniently used to reduce AZT-induced bone marrow toxicity. [References: 31]
机译:锌和N-乙酰半胱氨酸(NAC)在保护造血祖细胞免受齐多夫定(AZT)诱导的毒性作用中已得到研究。在存在和不存在乙酸锌(100μM)或NAC(100μM)的情况下,将鼠骨髓祖细胞(BMPC,1 x 10(6))暴露于各种浓度(0.1-50μM)的AZT。细胞存活通过红系(CFU-E)和粒细胞(CEU-GM)谱系的集落形成测定来确定。在锌的存在下,AZT的IC50值在CFU-E分析中提高了约3倍(从3.0到9.5μM),在CFU-GM分析中提高了7倍(从4.3到28.8μM)。在NAC的存在下,IC50值分别增加了2倍和4倍。为了描述锌对BMPC的显着保护机制,使用31-mer cDNA探针监测了金属硫蛋白(MT)的mRNA水平。锌导致BMPC中MT mRNA水平的浓度依赖性增加。这些结果表明锌和NAC膳食补充剂可方便地用于减少AZT诱导的骨髓毒性。 [参考:31]

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