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

Publication date: Available online 6 November 2019Source: Journal of Pharmaceutical AnalysisAuthor(s): Ningning Zheng, Yu Gu, Ying Hong, Lili Sheng, Linlin Chen, Feng Zhang, Zimiao Weng, Weidong Zhang, Zean Zhang, Wei Jia, Houkai LiAbstractLiver 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 reveal 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
Source: Journal of Pharmaceutical Analysis - Category: Drugs & Pharmacology Source Type: research