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

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. Graphical abstract Image 1 Highlights • Vac pretreatment attenuated AP-induced liver injury in rats.• Vac pretreatment elevated metabolite 2-HB both in cecum and serum.• 2-HB attenuated the AP-induced hepatotoxicity both in vitro and in vivo.

SUBMITTER: Zheng N 

PROVIDER: S-EPMC7775853 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature