Effect of glucocorticoid pretreatment on oxidative liver injury and survival in jaundiced rats with endotoxin cholangitis.
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.
Lee
Chi Wei
CW
Department of Emergency Medicine, E-Da Hospital, I-Shou University, 1 E-Da Road, Jiau-shu Tsuen, Yan-chau Shiang, 824, Kaohsiung, Taiwan.
Chuang
Jiin Haur
JH
Wang
Pei Wen
PW
Chang
Nyuk Kong
NK
Wang
Hsiu Chuan
HC
Huang
Chao Cheng
CC
Tiao
Mao Meng
MM
Lo
Sing Kai
SK
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
D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D015846:Monokines; D003907:Dexamethasone