An added value of Azithromycin: mitigation of Doxorubicin associated oxidative damage and genotoxicity in normal human bronchial epithelium cells.

IF 2.5 4区 医学 Q3 GENETICS & HEREDITY Mutagenesis Pub Date : 2024-10-07 DOI:10.1093/mutage/geae024
Shaghayegh Shrokrzadeh, Shahrzad Moghim, Mohammad Shokrzadeh, Shaghayegh Aghajanshakeri
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Abstract

Doxorubicin, a well-known and widely used antineoplastic agent with direct ROS-accumulating activity, has proven effective in treating various cancer types. However, its non-specific cytotoxicity towards non-cancerous cells prompts concerns regarding potential adverse effects. Azithromycin is an antibiotic for treating bacterial infections and an anti-inflammatory agent, particularly beneficial in managing respiratory conditions like bronchitis and sinusitis. Despite azithromycin's well-documented antibacterial properties, its potential cellular/genomic protective effects remain unexplored. As an in vitro model, BEAS-2B cells (normal human bronchial epithelium cells) were employed in the present study to assess whether azithromycin possesses any protective properties against doxorubicin-induced cellular toxicity. Cells in pre-treatment culture were treated to various amounts of azithromycin (3.125, 6.25, 12.5, 25, and 50 μg/mL) in combination with doxorubicin at IC50 (0.08 μg/mL). Doxorubicin at 0.08 μg/mL highlighted cytotoxicity, oxidative stress, and genotoxicity. Azithromycin at 25 and 50 μg/mL markedly modulated oxidative stress and genomic damage by decreasing the ROS and LPO amounts, and suppressing DNA fragmentation in the comet assay parameters. Consequently, azithromycin may be regarded as a cytomodulating, antigenotoxic, and antioxidant agent.

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阿奇霉素的附加值:减轻与多柔比星相关的氧化损伤和正常人支气管上皮细胞的基因毒性。
多柔比星是一种众所周知且广泛使用的抗肿瘤药物,具有直接积累 ROS 的活性,已被证明能有效治疗各种癌症类型。然而,多柔比星对非癌细胞的非特异性细胞毒性引起了人们对其潜在不良影响的担忧。阿奇霉素是一种治疗细菌感染的抗生素,也是一种消炎药,对治疗支气管炎和鼻窦炎等呼吸道疾病特别有效。尽管阿奇霉素的抗菌特性已得到充分证实,但其潜在的细胞/基因组保护作用仍有待探索。本研究以 BEAS-2B 细胞(正常人支气管上皮细胞)为体外模型,评估阿奇霉素是否对多柔比星诱导的细胞毒性具有保护作用。在预处理培养中,细胞接受不同剂量的阿奇霉素(3.125、6.25、12.5、25 和 50 μg/mL)与 IC50(0.08 μg/mL)的多柔比星联合处理。0.08 微克/毫升的多柔比星突出了细胞毒性、氧化应激和遗传毒性。25 和 50 μg/mL 的阿奇霉素通过降低 ROS 和 LPO 的含量以及抑制彗星试验参数中的 DNA 断裂,明显调节了氧化应激和基因组损伤。因此,阿奇霉素可被视为一种细胞调节剂、抗原毒剂和抗氧化剂。
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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
期刊介绍: Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.
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