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槲皮素对依托泊苷诱导的大鼠骨髓细胞氧化DNA损伤和骨髓抑制的影响。

The effect of quercetin on oxidative DNA damage and myelosuppression induced by etoposide in bone marrow cells of rats.

作者信息

Papież Monika A

机构信息

Department of Cytobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.

出版信息

Acta Biochim Pol. 2014;61(1):7-11. Epub 2014 Mar 17.

Abstract

There is increasing evidence for the existence of an association between the presence of etoposide phenoxyl radicals and the development of treatment-related acute myeloid leukemia (t-AML), which occurs in a few percent of patients treated with this chemotherapeutic agent. The most common side effect caused by etoposide is myelosuppression, which limits the use of this effective drug. The goal of the study was to investigate the influence of antioxidant querectin on myelosuppression and oxidative DNA damage caused by etoposide. The influence of quercetin and/or etoposide on oxidative DNA damage was investigated in LT-12 cell line and bone marrow cells of rats via comet assay. The effect of quercetin on myelosuppression induced by etoposide was invetsigated by cytological analysis of bone marrow smears stained with May-Grünwald-Giemsa stain. Etoposide caused a significant increase in oxidative DNA damage in bone marrow cells and LT-12 cell line in comparison to the appropriate controls. Quercetin significantly reduced the oxidative DNA damage caused by etoposide both in vitro and in vivo. Quercetin also significantly protected against a decrease in the percentage of myeloid precursors and erythroid nucleated cells caused by etoposide administration in comparison to the group treated with etoposide alone. The results of the study indicate that quercetin could be considered a protectively acting compound in bone marrow cells during etoposide therapy.

摘要

越来越多的证据表明,依托泊苷苯氧自由基的存在与治疗相关的急性髓系白血病(t-AML)的发生之间存在关联,这种白血病发生在接受这种化疗药物治疗的少数患者中。依托泊苷最常见的副作用是骨髓抑制,这限制了这种有效药物的使用。本研究的目的是调查抗氧化剂槲皮素对依托泊苷引起的骨髓抑制和氧化性DNA损伤的影响。通过彗星试验在LT-12细胞系和大鼠骨髓细胞中研究了槲皮素和/或依托泊苷对氧化性DNA损伤的影响。通过对用美-格-姬氏染色法染色的骨髓涂片进行细胞学分析,研究了槲皮素对依托泊苷诱导的骨髓抑制的作用。与相应对照组相比,依托泊苷导致骨髓细胞和LT-12细胞系中的氧化性DNA损伤显著增加。槲皮素在体外和体内均显著降低了依托泊苷引起的氧化性DNA损伤。与单独使用依托泊苷治疗的组相比,槲皮素还显著保护了由依托泊苷给药引起的髓系前体细胞和有核红细胞百分比的降低。研究结果表明,在依托泊苷治疗期间,槲皮素可被认为是一种对骨髓细胞有保护作用的化合物。

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