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药物安乃近钠对体外培养的非洲绿猴肾(Vero)细胞系的遗传毒性和细胞毒性作用。

Genotoxic and cytotoxic effects of the drug dipyrone sodium in African green monkey kidney (Vero) cell line exposed in vitro.

作者信息

Gomes Lorena M, Moysés Daniele A, Nascimento Henrique F S, Mota Tatiane C, Bonfim Lais T, Cardoso Plínio C S, Burbano Rommel M R, Bahia Marcelo O

机构信息

Laboratory of Human Cytogenetic, Institute of Biological Sciences, Federal University of Pará (UFPA), Av. Augusto Corrêa, 01, Belém, Pará, 66075-110, Brazil.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul;394(7):1529-1535. doi: 10.1007/s00210-021-02078-2. Epub 2021 Mar 23.

Abstract

Dipyrone or metamizole is one of the most used analgesics, mainly due to its low financial cost. However, in some countries, the sale of dipyrone is prohibited due to reported severe cases of agranulocytosis as a result of its use. Despite its high use, studies showing genotoxic and cytotoxic effects of dipyrone in mammalian cells are scarce. Therefore, in the present study, we assessed cell viability, genotoxic effects, cytotoxic effects (by apoptosis and necrosis induction), and the induction of reactive oxygen species (ROS) in Vero cells (a cell line obtained from the red kidney of green monkey) exposed to dipyrone. Our results showed a significant reduction in viability of cells exposed to dipyrone by the MTT assay. A significant increase in damage index evaluated by a comet assay was also observed, which indicates its genotoxic effects. In which concerns the cytotoxic effects of dipyrone, we observed a significant increase in the number of apoptotic cells using fluorescent dyes after 24 h and 48 h of treatment with the drug. Our results also showed that there was no significant difference in the induction of ROS generation after treatment of the cells with the drug assessed by the DCFH-DA assay. Thus, our work showed that dipyrone is both a genotoxic and cytotoxic drug to Vero cells in the assessed conditions.

摘要

安乃近或甲氨基安替比林是最常用的镇痛药之一,主要因其成本低廉。然而,在一些国家,由于有报道称使用安乃近会导致严重的粒细胞缺乏症病例,因此安乃近的销售被禁止。尽管其使用广泛,但关于安乃近在哺乳动物细胞中遗传毒性和细胞毒性作用的研究却很少。因此,在本研究中,我们评估了暴露于安乃近的非洲绿猴肾细胞(Vero细胞系)的细胞活力、遗传毒性作用、细胞毒性作用(通过诱导凋亡和坏死)以及活性氧(ROS)的产生。我们的结果表明,通过MTT法检测,暴露于安乃近的细胞活力显著降低。通过彗星试验评估的损伤指数也显著增加,这表明其具有遗传毒性作用。关于安乃近的细胞毒性作用,在用该药物处理24小时和48小时后,使用荧光染料观察到凋亡细胞数量显著增加。我们的结果还表明,通过DCFH-DA试验评估,在用该药物处理细胞后,ROS产生的诱导没有显著差异。因此,我们的研究表明,在评估条件下,安乃近对Vero细胞既是一种遗传毒性药物,也是一种细胞毒性药物。

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