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

作　　者：Ningning Zheng Yu Gu Ying Hong Lili Sheng Linlin Chen Feng Zhang Jie Hou Weidong Zhang Zean Zhang Wei Jia Houkai Li 

机构地区：[1]Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [2]College of Basic Medical Sciences,Dalian Medical University,Dalian,116044,China [3]School of Pharmacy,Second Military Medical University,Shanghai,200433,China [4]Center for Drug Safety Evaluation and Research,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [5]University of Hawaii Cancer Center,Honolulu,HI,96813,USA [6]Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai,200233,China

出　　处：《Journal of Pharmaceutical Analysis》2020年第6期560-570,共11页药物分析学报（英文版）

基　　金：the National Natural Science Foundation of China(No.81873059&81673662);the National Key Research and Development Program of China(No.2017YFC1700200);Shuguang Scholar(16SG36)at Shanghai Institutions of Higher Learning from Shanghai Municipal Education Commission。

摘　　要：Liver injury caused by acetaminophen(AP)overdose is a leading public health problem.Although APinduced 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.

关 键 词：REVEALED Liver injury Gut microbiota ACETAMINOPHEN VANCOMYCIN 2-Hydroxybutyric acid 

分 类 号：R96[医药卫生—药理学]