Gallic Acid Attenuates Sepsis-Induced Liver Injury through C/EBPβ-Dependent MAPK Signaling Pathway.

Abstract

Liver injury is a major complication associated with sepsis. Together with others, the study has shown that gallic acid (GA) exerts anti-inflammatory and antioxidant effects in vivo. However, the role of GA in sepsis-mediated hepatic impairment and the underlying mechanisms remains to be elucidated. C57BL/6J mice are pretreated with saline or GA and subjected to sham or cecal ligation and puncture (CLP). The pathological alterations are assessed by hematoxylin and eosin staining as well as immunohistochemical staining. RNA sequencing is employed to analyze hepatic transcriptome modifications. The study finds that GA supplementation significantly ameliorates CLP-induced mortality, liver dysfunction, and inflammation. RNA sequencing reveals that 1324 genes are markedly differentially regulated in livers of saline- or GA-treated sham or CLP mice. Gene ontology analysis demonstrates that the differentially expressed genes regulated by GA are predominantly correlated with the immune system process, oxidation-reduction process, and inflammatory response. Furthermore, mitogen-activated protein kinase (MAPK) signaling is localized in the center of the GA-mediated pathway network. Notably, activation of MAPK by C16-PAF significantly blocks GA-mediated protective effects on hepatic injury, inflammation, as well as CCAAT/enhancer-binding protein-β (C/EBPβ) dependent extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling. Therefore, this study indicates that GA may offer a promising therapeutic opportunity for sepsis-associated liver injury.