Silver-based antimicrobials are widely used topically to treat infections associated with multi-drug resistant (MDR) pathogens. Expanding this topical use to aerosols to treat lung infections requires understanding and preventing silver toxicity in the respiratory tract. A key mechanism resulting in silver-induced toxicity is the production of reactive oxygen species (ROS). In this study, we have verified ROS generation in silver-treated bronchial epithelial cells prompting evaluation of three antioxidants, N-acetyl cysteine (NAC), ascorbic acid, and melatonin, to identify potential prophylactic agents. Among them, NAC was the only candidate that abrogated the ROS generation in response to silver acetate exposure resulting in the rescue of these cells from silver-associated toxicity. Further, this protective effect directly translated to preservation of metabolic activity, as demonstrated by the normal levels of citric acid cycle metabolites in NAC-pretreated silver acetate-exposed cells. Because the citric acid cycle remained functional, silver-exposed cells pre-incubated with NAC demonstrated significantly higher levels of adenosine triphosphate levels compared with NAC-free controls. Moreover, we found that this prodigious capacity of NAC to rescue silver acetate-exposed cells was due not only to its antioxidant activity, but also to its ability to directly bind silver. Despite binding to silver, NAC did not alter the antimicrobial activity of silver acetate.

中文翻译：

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N-乙酰半胱氨酸消除人体细胞中银诱导的活性氧，而不改变银基抗菌活性


银基抗菌剂广泛用于局部治疗与多重耐药 (MDR) 病原体相关的感染。将这种局部用途扩展​​到治疗肺部感染的气雾剂需要了解和预防呼吸道中的银毒性。导致银毒性的一个关键机制是活性氧 (ROS) 的产生。在这项研究中，我们验证了银处理的支气管上皮细胞中 ROS 的生成，从而促进对三种抗氧化剂 N-乙酰半胱氨酸 (NAC)、抗坏血酸和褪黑激素的评估，以确定潜在的预防药物。其中，NAC 是唯一能够响应醋酸银暴露而消除 ROS 生成的候选药物，从而使这些细胞免受银相关毒性的影响。此外，这种保护作用直接转化为代谢活性的保存，正如 NAC 预处理的醋酸银暴露细胞中柠檬酸循环代谢物的正常水平所证明的那样。由于柠檬酸循环仍然发挥作用，与不含 NAC 的对照相比，与 NAC 预孵育的银暴露细胞显示出显着更高的三磷酸腺苷水平。此外，我们发现 NAC 拯救暴露于醋酸银的细胞的惊人能力不仅归因于其抗氧化活性，还归因于其直接结合银的能力。尽管与银结合，NAC 并没有改变醋酸银的抗菌活性。