title: Levobupivacaine inhibits lipopolysaccharide-induced high mobility group box 1 release in vitro and in vivo.
abstract: BACKGROUND
  The aim of the study was to investigate whether levobupivacaine (LB) suppressed lipopolysaccharide (LPS)-induced high mobility group box 1 (HMGB1) release in vitro and in vivo, and to determin its molecular mechanisms of action.
  
  
  METHODS
  RAW264.7 cells were treated with LPS and LB for 24 h. Levels of HMGB1, nuclear factor-kappa B (NF-κB) and phosphorylated p38 mitogen-activated protein kinase (MAPK) were measured by Enzyme-linked immunosorbent assay and Western blotting; the levels of HMGB1 messenger RNA were measured by real-time polymerase chain reaction. In addition, cecal ligation and puncture-induced septic C57BL/6 received LB infusion, and the levels of HMGB1 and functional parameters of multiple organs determined using several detection kits.
  
  
  RESULTS
  LB inhibited HMGB1 release in vitro and in vivo. Furthermore, LB inhibited the translocation of NF-κB and phosphorylation of p38 MAPK in vitro. Mice treated with LB infusion improved survival in mice and significantly reduced cecal ligation and puncture-induced dysfunction of organs.
  
  
  CONCLUSIONS
  LB suppresses LPS-induced HMGB1 release in vitro and in vivo by partially inhibiting NF-κB/p38 MAPK pathways. LB can rescue mice from sepsis and protect against organ dysfunction in septic mice.
authors.affiliation: Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Yunfen
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China. Electronic address: shuangfeihu666@outlook.com.
authors.forename: Shuangfei
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Leping
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D019610:Cytoprotection / Q000187:drug effects; D004347:Drug Interactions; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D000077554:Levobupivacaine; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018805:Sepsis / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000077554:Levobupivacaine; D048051:p38 Mitogen-Activated Protein Kinases; D002045:Bupivacaine
keywords: HMGB1; Lipopolysaccharides; NF-κB; Sepsis; levobupivacaine; p38 MAPK