2. Academic Validation
  3. Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid

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

  • J Pharm Anal. 2020 Dec;10(6):560-570. doi: 10.1016/j.jpha.2019.11.003.
Ningning Zheng 1,  Yu Gu 1,  Ying Hong 1,  Lili Sheng 1,  Linlin Chen 1,  Feng Zhang 1,  Jie Hou 2,  Weidong Zhang 1 3,  Zean Zhang 4,  Wei Jia 5 6,  Houkai Li 1
Affiliations

Affiliations

  • 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.
PMID: 33425450 DOI: 10.1016/j.jpha.2019.11.003
Abstract

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.

Keywords

2-Hydroxybutyric acid; Acetaminophen; Gut microbiota; Liver injury; Vancomycin; revealed.

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