title: Pretreatment with wortmannin alleviates lipopolysaccharide/d-galactosamine-induced acute liver injury.
abstract: Intestinal endotoxemia-induced liver injury is a common clinical disease which leads to liver failure and death. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, could be used for suppressing autophagy in vitro and in vivo. Autophagy is an evolutionarily conserved and lysosome dependent protein degradation pathway, which participates in various physiological and pathological processes. The present study aims to explore the effect of pretreatment with wortmannin on acute liver injury and the autophagy in acute liver injury. We demonstrated that wortmannin could downregulate the expression of phosphorylated extracellular regulated protein kinase and p65, decrease the production and release of hepatic inflammatory cytokines, and then reduce hepatocytes apoptosis and necrosis. More importantly, we found that autophagy was induced to increase in LPS/D-GalN-induced acute liver injury, and pretreatment with wortmannin could effectively inhibit increased autophagy in acute liver injury. In conclusion, these results indicate that wortmannin plays a protective role in LPS/D-GalN induced hepatocytotoxity maybe by inhibiting autophagy and could be acted as a target for the treatment of acute liver injury.
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Zengtao
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Infection, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: Hongju
authors.initials: H
authors.lastname: Mao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, PR China; Department of Children's Medical Laboratory Diagnosis Center, Qilu Children's Hospital of Shandong University, Jinan, Shandong, PR China.
authors.forename: Xingli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, PR China. Electronic address: wxy990809@163.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001343:Autophagy; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D005688:Galactosamine / Q000009:adverse effects*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D008070:Lipopolysaccharides / Q000009:adverse effects*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009336:Necrosis; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D016207:Cytokines; D008070:Lipopolysaccharides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077191:Wortmannin
keywords: Acute liver injury; Autophagy; Lipopolysaccharide; Wortmannin; d-Galactosamine