Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid

• 作者: Feng Zhang Houkai Li Jie Hou Lili Sheng Linlin Chen Ningning Zheng Wei Jia Weidong Zhang Ying Hong Yu Gu Zean Zhang
• 来源期刊: 药物分析学报（英文）
• 年，卷（期）: 2020,（6）
• 所属期刊栏目: Original Articles
• 页码范围: 560-570
• 页数: 11页
• 语种: 英文

摘要

Liver injury caused by acetaminophen (AP) overdose is a leading public health problem. Although AP-induced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone (NAPQI), a toxic metabolite of AP, resulting in cell damage, emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota. However, the gut microbiota-involved mechanism remains largely unknown. In our study, we found that vancomycin (Vac) pretreatment (100 mg/kg, twice a day for 4 days) attenuated AP-induced liver injury, altered the composition of gut microbiota, and changed serum metabolic profile. Moreover, we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid (2-HB), which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels. Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.