title: Effect of glucocorticoid pretreatment on oxidative liver injury and survival in jaundiced rats with endotoxin cholangitis.
abstract: BACKGROUND
  Biliary tract infection is associated with high mortality. This study investigated the effect of glucocorticoid pretreatment on lipopolysaccharide (LPS)-induced cholangitis.
  
  
  METHODS
  Rats undergoing either sham operation or ligation of the extrahepatic bile duct (BDL) for 2 weeks were randomly assigned to receive intravenous injections of dexamethasone (DX) or normal saline (NS) prior to infusing LPS into the biliary tract. The plasma levels of tumor necrosis factor-alpha (TNFalpha), chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) as well as liver mRNA expression of MCP-1 and MIP-2 were determined. Infiltration of monocytes, Kupffer cells, and neutrophils in rat liver were studied with immunohistochemistry. Oxidative liver injury was measured by the malondialdehyde (MDA) content.
  
  
  RESULTS
  Dexamethasone pretreatment resulted in significantly decreased plasma levels of TNFalpha at 1 hour, MCP-1 and MIP-2 at 2 and 3 hours, and decreased liver MCP-1 mRNA expression at 3 hours following LPS infusion in BDL-DX rats than in BDL-NS rats. The number of inflammatory cells in the liver was significantly different between sham- and BDL-treated rats but was not affected by DX pretreatment. Pretreatment with DX resulted in significantly decreased liver MDA contents in the BDL-DX group than that in the BDL-NS group. Jaundiced rats pretreated with 5 mg DX prior to infusion of 1 g of LPS were 6.8 times more likely to survive than those that were not pretreated.
  
  
  CONCLUSIONS
  Pretreatment of jaundiced, LPS-treated rats with a supraphysiological dose of dexamethasone may rescue their lives by suppression of chemokine expression and alleviation of oxidative liver injury.
authors.affiliation: Department of Emergency Medicine, E-Da Hospital, I-Shou University, 1 E-Da Road, Jiau-shu Tsuen, Yan-chau Shiang, 824, Kaohsiung, Taiwan.
authors.forename: Chi Wei
authors.initials: CW
authors.lastname: Lee
authors.forename: Jiin Haur
authors.initials: JH
authors.lastname: Chuang
authors.forename: Pei Wen
authors.initials: PW
authors.lastname: Wang
authors.forename: Nyuk Kong
authors.initials: NK
authors.lastname: Chang
authors.forename: Hsiu Chuan
authors.initials: HC
authors.lastname: Wang
authors.forename: Chao Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Mao Meng
authors.initials: MM
authors.lastname: Tiao
authors.forename: Sing Kai
authors.initials: SK
authors.lastname: Lo
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054426:Chemokine CXCL2; D002761:Cholangitis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003907:Dexamethasone / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000627:therapeutic use*; D007565:Jaundice / Q000209:etiology / Q000401:mortality*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015846:Monokines / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate
chemical_list: D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D015846:Monokines; D003907:Dexamethasone