PMID- 17102917 OWN - NLM STAT- MEDLINE DCOM- 20070406 LR - 20181113 IS - 0364-2313 (Print) IS - 0364-2313 (Linking) VI - 30 IP - 12 DP - 2006 Dec TI - Effect of glucocorticoid pretreatment on oxidative liver injury and survival in jaundiced rats with endotoxin cholangitis. PG - 2217-26 AB - INTRODUCTION: 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. FAU - Lee, Chi Wei AU - Lee CW AD - Department of Emergency Medicine, E-Da Hospital, I-Shou University, 1 E-Da Road, Jiau-shu Tsuen, Yan-chau Shiang, 824, Kaohsiung, Taiwan. FAU - Chuang, Jiin Haur AU - Chuang JH FAU - Wang, Pei Wen AU - Wang PW FAU - Chang, Nyuk Kong AU - Chang NK FAU - Wang, Hsiu Chuan AU - Wang HC FAU - Huang, Chao Cheng AU - Huang CC FAU - Tiao, Mao Meng AU - Tiao MM FAU - Lo, Sing Kai AU - Lo SK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - World J Surg JT - World journal of surgery JID - 7704052 RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL2) RN - 0 (Glucocorticoids) RN - 0 (Lipopolysaccharides) RN - 0 (Monokines) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Animals MH - Chemokine CCL2/biosynthesis MH - Chemokine CXCL2 MH - Cholangitis/complications/*metabolism/pathology MH - Dexamethasone/*therapeutic use MH - Glucocorticoids/*therapeutic use MH - Jaundice/etiology/*mortality MH - Lipopolysaccharides/administration & dosage MH - Liver/*drug effects/metabolism MH - Male MH - Monokines/biosynthesis MH - Oxidative Stress/*drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Survival Rate EDAT- 2006/11/15 09:00 MHDA- 2007/04/07 09:00 CRDT- 2006/11/15 09:00 PHST- 2006/11/15 09:00 [pubmed] PHST- 2007/04/07 09:00 [medline] PHST- 2006/11/15 09:00 [entrez] AID - 10.1007/s00268-006-0143-0 [doi] PST - ppublish SO - World J Surg. 2006 Dec;30(12):2217-26. doi: 10.1007/s00268-006-0143-0.