Abstract Drug-induced liver injury (DILI) is the predominant cause of acute liver failure in many countries, which is closely associated with reactive oxygen species (ROS) and inflammation. Although N-acetylcysteine (NAC) is presently the first-choice antidote for DILI, it often fails to benefit the late stage patients due to its narrow therapeutic time window. Herein, we report ceria nanozymes (CeNZs) that simultaneously scavenge reactive oxygen species and generate oxygen for the treatment of acetaminophen-induced liver injury (a typical form of DILI), enabling a prolonged therapeutic time window as compared to NAC. It is found that CeNZs can effectively scavenge ROS in impaired hepatocytes for detoxification. More importantly, CeNZs can generate abundant oxygen based on their catalase (CAT)-mimic activity, thus further alleviating hypoxia and specifically inhibiting the pro-inflammatory macrophages to relieve inflammation for a promoted hepatocyte regeneration of DILI, which is vital for the treatment of late stage DILI when there is already massive hepatocyte necrosis. The dual detoxification and inflammatory regulation by CeNZs for DILI treatment with relatively long therapeutic time window as compared to NAC, together with the revealed mechanism herein, suggesting the future clinical use of CeNZs for DILI treatment, especially for the late stage DILI treatment.

中文翻译：

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二氧化铈纳米酶的双重解毒和炎症调节用于药物性肝损伤治疗

摘要 药物性肝损伤（DILI）是许多国家急性肝衰竭的主要原因，其与活性氧（ROS）和炎症密切相关。尽管 N-乙酰半胱氨酸 (NAC) 目前是 DILI 的首选解毒剂，但由于其治疗时间窗口狭窄，它往往无法使晚期患者受益。在此，我们报告了氧化铈纳米酶 (CeNZs)，它同时清除活性氧并产生氧气，用于治疗对乙酰氨基酚引起的肝损伤（DILI 的一种典型形式），与 NAC 相比能够延长治疗时间窗口。发现CeNZs可以有效清除受损肝细胞中的ROS以进行解毒。更重要的是，CeNZs 可以根据它们的过氧化氢酶 (CAT) 模拟活性产生丰富的氧气，从而进一步缓解缺氧并特异性抑制促炎巨噬细胞以缓解炎症，促进 DILI 的肝细胞再生，这对于已经存在大量肝细胞坏死的晚期 DILI 的治疗至关重要。与 NAC 相比，CeNZs 对 DILI 治疗的双重解毒和炎症调节具有相对较长的治疗时间窗，以及本文揭示的机制，表明 CeNZs 未来用于 DILI 治疗的临床应用，尤其是晚期 DILI 治疗。