Liping Cao1, Zhenghong Li2, Zhizhou Yang3, Mengmeng Wang3, Wei Zhang3, Yi Ren3, Liang Li3, Junxian Hu3, Zhaorui Sun4, Shinan Nie5. 1. Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China; Nanjing University of Chinese Medicine, Nanjing 210023, PR China. 2. Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China. 3. Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. 4. Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address: sunzhr84@163.com. 5. Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address: shn_nie@sina.com.
Abstract
AIMS: Ferulic acid (FA) is a component found in plants that has free radical scavenging and liver-protective properties. Acute liver injury (ALI) is a serious complication of sepsis and is closely associated with changes in the levels of inflammatory factors. This study was taken to examine the role of FA in cecal ligation and perforation (CLP)-induced murine ALI and lipopolysaccharide (LPS)-induced cellular ALI models. MATERIALS AND METHODS: An in vivo ALI model was established by performing CLP surgery on C57BL/6 mice. After the ALI model was established, mice were examined for liver injury, including HE staining to observe tissue sections, the percentage of liver/body weight and inflammatory factor levels. Myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured in liver or serum using commercial kits. An in vitro ALI model was established using LPS-stimulated RAW264.7 cells. Cell viability was measured by MTT method and the intracellular levels of IL-10, IL-1β, IL-6, IL-12 and TNF-α inflammatory factors were measured using kits. The expression of GSK-3β, NF-κB and CREB was measured by western blot or immunofluorescence. KEY FINDINGS: FA pretreatment significantly reduced liver/body weight ratio, decreased MPO, AST and ALT activity, alleviated the inflammatory responses and improved CLP-induced histopathological changes in liver. In addition, in vitro results showed that FA could dose-dependently increase the viability of RAW264.7 cells and decrease the levels of pro-inflammatory factors. SIGNIFICANCE: In conclusion, our data suggest that FA can ameliorate ALI-induced inflammation via the GSK-3β/NF-κB/CREB pathway, suggesting that FA can be used to protect the liver against ALI.
AIMS: Ferulic acid (FA) is a component found in plants that has free radical scavenging and liver-protective properties. Acute liver injury (ALI) is a serious complication of sepsis and is closely associated with changes in the levels of inflammatory factors. This study was taken to examine the role of FA in cecal ligation and perforation (CLP)-induced murine ALI and lipopolysaccharide (LPS)-induced cellular ALI models. MATERIALS AND METHODS: An in vivo ALI model was established by performing CLP surgery on C57BL/6 mice. After the ALI model was established, mice were examined for liver injury, including HE staining to observe tissue sections, the percentage of liver/body weight and inflammatory factor levels. Myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured in liver or serum using commercial kits. An in vitro ALI model was established using LPS-stimulated RAW264.7 cells. Cell viability was measured by MTT method and the intracellular levels of IL-10, IL-1β, IL-6, IL-12 and TNF-α inflammatory factors were measured using kits. The expression of GSK-3β, NF-κB and CREB was measured by western blot or immunofluorescence. KEY FINDINGS: FA pretreatment significantly reduced liver/body weight ratio, decreased MPO, AST and ALT activity, alleviated the inflammatory responses and improved CLP-induced histopathological changes in liver. In addition, in vitro results showed that FA could dose-dependently increase the viability of RAW264.7 cells and decrease the levels of pro-inflammatory factors. SIGNIFICANCE: In conclusion, our data suggest that FA can ameliorate ALI-induced inflammation via the GSK-3β/NF-κB/CREB pathway, suggesting that FA can be used to protect the liver against ALI.