title: A novel acute lethal liver injury mouse model with visualization of NF-κB activity for treatment of severe acute liver injury.
abstract: Acute lethal inflammation, especially that related to liver injury, is an important clinical issue. To date, however, there is no model that can be used to assess this serious condition. This study was designed to establish a novel lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute lethal liver injury model in nuclear factor-κB (NF-κB) transgenic mice. The results show that a high dose of LPS (500 μg/kg) plus D-GalN (800 mg/kg) successfully established a novel mouse model of acute lethal liver injury with a lifespan of 8-10 h. Significantly increased NF-κB activity, detected with anin vivoimaging system (IVIS), peaked at approximately 4 h post-LPS/D-GalN challenge in NF-κB transgenic mice. Moreover, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 were significantly increased and peaked at approximately 4 h post-i.p.injection of LPS/D-GalN. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) also sharply increased. Correlation analyses showed that NF-κB activity was significantly correlated with serum levels of ALT and AST. The mouse model livers showed marked congestion and hemorrhage, and hematoxylin and eosin (H&E) staining confirmed the destruction of the lobular structure and severe hepatocyte necrosis and hemorrhage. None of these changes were observed in the control mice. In summary, a novel LPS/D-GalN-induced acute lethal liver injury model with visualization of NF-κB activity was established in NF-κB transgenic mice. This model will provide the technology for developing new therapeutic strategies for treatment of severe acute liver injury complicated by endotoxemia or septicemia.
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical University Zhanjiang 524001, China.
authors.forename: Huanjin
authors.initials: H
authors.lastname: Liao
authors.affiliation: Institute of Nephrology, Affiliated Hospital of Guangdong Medical University Zhanjiang 524001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical University Zhanjiang 524001, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Nephrology, Affiliated Hospital of Guangdong Medical University Zhanjiang 524001, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical University Zhanjiang 524001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Rheumatism and Immunology, Affiliated Hospital of Guangdong Medical University Zhanjiang 524001, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Xie
authors.affiliation: Institute of Nephrology, Affiliated Hospital of Guangdong Medical University Zhanjiang 524001, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Pan
keywords: Liver injury; alanine aminotransferase (ALT); lipopolysaccharide/galactosamine (LPS/D-GalN); nuclear factor-κB (NF-κB)