title: LPS pretreatment ameliorates D-galactosamine/lipopolysaccharide-induced acute liver failure in rat.
abstract: Acute liver failure (ALF) remains an extremely poor prognosis and high mortality; with no effective treatments. The endotoxin tolerance (ET) phenotype has been reported to exhibit protective activities in several sepsis models. We now investigated the effects and underlying intraperitoneal injection of the same volume of pyrogen-free 0.9% sodium chloride instead of LPS for five consecutive days before D-GalN/LPS injection in rats. The serum levels of TNF-α, IL-6, ALT, AST and TBiL from ET + ALF group and ALF group were measured at different time points. Our results showed that ET + ALF group markedly reduced the serum levels of TNF-α, IL-6, ALT, AST and TBiL and histological features in the ET + ALF group were improved significantly. Furthermore, LPS pre-treatment inhibited D-GalN/LPS-induced NF-κB activation, Bax activation, signal transducer and activator of transcription-1 (STAT1) and signal transducer and activator of transcription-3 (STAT3) activities. LPS pre-treatment also significantly enhance the expression of suppressors of cytokine signaling 1 (SOCS1) and suppressors of cytokine signaling 3 (SOCS3). Our experimental data indicated that ET might alleviate D-GalN/LPS-induced ALF by inhibiting the inflammatory response, inactivation of STAT1 and STAT3 and up-regulation of SOCS1 and SOCS3.
authors.affiliation: Department of Intensive Care Unit, Ningbo First Hospital Ningbo, China.
authors.forename: Jin-Zhong
authors.initials: JZ
authors.lastname: Dong
authors.affiliation: Department of Infection Disease, Ningbo First Hospital Ningbo, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: Department of Infection Disease, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, China.
authors.forename: Sai-Nan
authors.initials: SN
authors.lastname: Zhang
authors.affiliation: Department of Infection Disease, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, China.
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Shi
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Shao-Long
authors.initials: SL
authors.lastname: Chen
authors.affiliation: Department of Infection Disease, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, China.
authors.forename: Nai-Bin
authors.initials: NB
authors.lastname: Yang
authors.affiliation: Department of Infection Disease, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, China.
authors.forename: Shun-Lan
authors.initials: SL
authors.lastname: Ni
authors.affiliation: Department of Intensive Care Unit, Ningbo First Hospital Ningbo, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhu
authors.affiliation: Department of Infection Disease, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, China.
authors.forename: Ming-Qin
authors.initials: MQ
authors.lastname: Lu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology; D005688:Galactosamine / Q000009:adverse effects; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017114:Liver Failure, Acute / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013047:Specific Pathogen-Free Organisms; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine
keywords: D-galactosamine; JAK/STAT; acute hepatic failure; inflammatory cytokines; lipoplysaccharide; rat