Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid
- Author:
Ningning ZHENG
1
;
Yu GU
;
Ying HONG
;
Lili SHENG
;
Linlin CHEN
;
Feng ZHANG
;
Jie HOU
;
Weidong ZHANG
;
Zean ZHANG
;
Wei JIA
;
Houkai LI
Author Information
1. Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China
- Keywords:
revealed;
Liver injury;
Gut microbiota;
Acetaminophen;
Vancomycin;
2-Hydroxybutyric acid
- From:
Journal of Pharmaceutical Analysis
2020;10(6):560-570
- CountryChina
- Language:Chinese
-
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.
