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Synergistic therapeutic efficacy of ebselen and silver ions against multidrug-resistant Acinetobacter baumannii-induced urinary tract infections.
Metallomics ( IF 3.4 ) Pub Date : 2020-05-12 , DOI: 10.1039/d0mt00091d
Chuanjiang Dong 1 , Jun Wang 2 , Huan Chen 1 , Peng Wang 3 , Jingxuan Zhou 4 , Ying Zhao 5 , Lili Zou 6
Affiliation  

Ebselen (EbSe), an organo-selenium compound with well-characterized toxicology and pharmacology, exhibited potent antibacterial activity against glutathione (GSH)-positive bacteria when combined with silver ions (Ag+). In this paper, the strong bactericidal activity of EbSe–Ag+ against multidrug-resistant (MDR) Acinetobacter baumannii has been confirmed, and its efficacy was mainly based on the inhibition of thioredoxin reductase (TrxR) activity and the depletion of the total GSH amount. Moreover, the therapeutic effect of EbSe–Ag+ on urinary tract infection was assessed in a mouse model induced with A. baumannii 0361# strain. The treatment with EbSe–Ag+ significantly reduced the bacterial load and expression levels of the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in bladder lesions; meanwhile, the pathological experiment showed that A. baumannii-induced changes in EbSe–Ag+ treated mice were much attenuated than that in the control group. Thus, all the results obtained here may lay the foundation for further analysis and development of EbSe–Ag+ as potential antibacterial agents for MDR A. baumannii-induced urinary tract infection treatment.

中文翻译:

依布硒啉和银离子对多重耐药鲍曼不动杆菌引起的尿路感染的协同治疗效果。

Ebselen (EbSe) 是一种具有良好毒理学和药理学特征的有机硒化合物,当与银离子 (Ag + )结合时,对谷胱甘肽 (GSH) 阳性细菌表现出强大的抗菌活性。在本文中,EbSe-Ag +对多重耐药(MDR)鲍曼不动杆菌的强杀菌活性得到证实,其功效主要基于抑制硫氧还蛋白还原酶(TrxR)活性和消耗总 GSH 量. 此外,在用鲍曼不动杆菌0361 #菌株诱导的小鼠模型中评估了 EbSe-Ag +对尿路感染的治疗效果。EbSe–Ag + 处理显着降低膀胱病变中促炎细胞因子白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)的细菌负荷和表达水平;同时,病理实验表明鲍曼不动杆菌引起的EbSe-Ag +处理小鼠的变化比对照组大大减弱。因此,这里获得的所有结果可能为进一步分析和开发 EbSe-Ag +作为耐多药鲍曼不动杆菌诱导的尿路感染治疗的潜在抗菌剂奠定基础。
更新日期:2020-06-25
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