Antibiotic resistance poses a great threat to human, animal and environmental health. β‐Lactam antibiotics have been successful in combating bacterial infections. However, the overuse, inappropriate prescribing, unavailability of new antibiotics and regulation barriers have exacerbated bacterial resistance to these antibiotics. 1,4,7‐Triazacyclononane (TACN) is a cyclic organic tridentate inhibitor with strong metal‐chelating abilities that has been shown to inhibit β‐lactamase enzymes and may represent an important breakthrough in the treatment of drug‐resistant bacterial strains. However, its cytotoxicity in the liver is unknown. This study aimed to determine the effect of TACN on oxidative stress in HepG2 cells. The HepG2 cells were treated with 0 to 500 µM TACN for 24 hours to obtain an IC₅₀ for use in subsequent assays. Free radicals were measured using the thiobarbituric acid reactive substance and nitric oxide synthase assays, respectively, while antioxidant levels were assessed using luminometry (glutathione [GSH] and adenosine triphosphate [ATP]) and Western blot analysis (SOD, catalase, GPx‐1, HSP70 and Nrf2). Percentage survival fluctuated as TACN concentration increased with a calculated IC₅₀ of 545 µM. A slight increase in HSP70 and Nrf2 expression indicated the presence of stress and a response against it, respectively. However, free radical production was not increased as indicated by decreased malondialdehyde levels and reactive nitrogen species. Glutathione levels increased slightly, while ATP levels were marginally altered. The results suggest that TACN does not induce oxidative stress in HepG2 cells and can be exploited as a potential inhibitor.

中文翻译：

---

1,4,7-三氮杂环壬烷对人肝细胞癌细胞（HepG2）氧化应激参数的分子影响。

抗生素抗性对人类，动物和环境健康构成巨大威胁。β-内酰胺抗生素已成功地抵抗了细菌感染。但是，过度使用，不适当的处方，无法使用新抗生素以及调节障碍都加剧了细菌对这些抗生素的耐药性。1,4,7-三氮杂双环壬烷（TACN）是一种具有强金属螯合能力的环状有机三齿抑制剂，已被证明可以抑制β-内酰胺酶，可能代表了对耐药细菌菌株的重要突破。但是，其在肝中的细胞毒性尚不清楚。这项研究旨在确定TACN对HepG2细胞氧化应激的影响。用0至500 µM TACN处理HepG2细胞24小时，获得IC ₅₀用于后续测定。使用硫代巴比妥酸反应性物质和一氧化氮合酶测定法分别测量自由基，而使用光度法（谷胱甘肽[GSH]和三磷酸腺苷[ATP]）和蛋白质印迹分析（SOD，过氧化氢酶，GPx-1， HSP70和Nrf2）。存活百分比随TACN浓度增加而波动，计算得出的IC ₅₀545 µM。HSP70和Nrf2表达的轻微增加分别表明存在压力和对其的反应。但是，丙二醛含量降低和活性氮含量降低表明，自由基的产生并未增加。谷胱甘肽水平略有增加，而ATP水平略有改变。结果表明，TACN不会在HepG2细胞中诱导氧化应激，可以用作潜在的抑制剂。