School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 510630, China.
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 510630, China.
Adv Sci (Weinh). 2023 Jun;10(16):e2206789. doi: 10.1002/advs.202206789. Epub 2023 Apr 10.
Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury and acute liver failure, while the detection, prognosis prediction, and therapy for APAP-induced liver injury (AILI) remain improved. Here, it is determined that the temporal pattern of circulating cell-free DNA (cfDNA) is strongly associated with damage and inflammation parameters in AILI. CfDNA is comparable to alanine aminotransferase (ALT) in predicting mortality and outperformed ALT when combined with ALT in AILI. The depletion of cfDNA or neutrophils alleviates liver damage, while the addition of cfDNA or adoptive transfer of neutrophils exacerbates the damage. The combination of DNase I and N-acetylcysteine attenuates AILI significantly. This study establishes that cfDNA is a mechanistic biomarker to predict mortality in AILI mice. The combination of scavenging cfDNA and reducing oxidative damage provides a promising treatment for AILI.
对乙酰氨基酚（APAP）过量是药物性肝损伤和急性肝衰竭的主要原因，而 APAP 诱导的肝损伤（AILI）的检测、预后预测和治疗仍有待改善。在这里，确定循环无细胞 DNA（cfDNA）的时间模式与 AILI 中的损伤和炎症参数密切相关。cfDNA 在预测死亡率方面与丙氨酸氨基转移酶（ALT）相当，并且在与 ALT 联合使用时优于 ALT 在 AILI 中的表现。cfDNA 或中性粒细胞的耗竭可减轻肝损伤，而 cfDNA 的添加或中性粒细胞的过继转移则可加重损伤。DNase I 和 N-乙酰半胱氨酸的联合使用可显著减轻 AILI。本研究确立了 cfDNA 是预测 AILI 小鼠死亡率的机制生物标志物。cfDNA 的清除和氧化损伤的减少相结合，为 AILI 的治疗提供了一种很有前途的方法。
