15-deoxy-delta(12-14)-prostaglandin-j2 and Liver-Failure--Acute

Acute obstructive cholangitis is a common disease with a high mortality rate. Ligands for peroxisome proliferator-activated receptor-gamma (PPARgamma), such as 15-deoxy-Delta(12,14)-prostaglandin J(2) (15D-PGJ(2)), have been proposed as a new class of anti-inflammatory compounds. This study investigated the effect of 15D-PGJ(2) treatment on lipopolysaccharide (LPS)-induced acute obstructive cholangitis. The rats were randomly assigned to five groups: sham operation (Sham; simple laparotomy), sham operation with intraperitoneal saline infusion (Sham+Saline), sham operation with intraperitoneal LPS infusion (Sham+LPS), bile duct ligation (BDL) with saline infusion into the bile duct (BDL+Saline), and BDL with LPS infusion into the bile duct (BDL+LPS). Biochemical assays of blood samples, histology of the liver, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were evaluated. Furthermore, the Sham+LPS and the BDL+LPS group were divided into two groups (with and without 15D-PGJ(2) treatment), and their survival rates were compared. Biochemical assays of blood samples, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were all significantly higher in the BDL+LPS group compared with those in the BDL+Saline group, indicating the presence of increased liver damage in the first group. However, preoperative administration of 15D-PGJ(2) significantly improved these outcomes. Furthermore, the survival rate after establishment of cholangitis was significantly improved by the administration of 15D-PGJ(2) in the BDL+LPS group. These results clearly demonstrate that 15D-PGJ(2) inhibits the inflammatory response and endothelial cell damage seen in acute obstructive cholangitis and could contribute to improve the outcome of this pathology.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Bile Ducts; Bilirubin; Cholangitis; Cholestasis, Extrahepatic; Disease Models, Animal; Endothelium, Vascular; Gene Expression; Hyaluronic Acid; Interleukin-6; Ligation; Lipopolysaccharides; Liver; Liver Circulation; Liver Failure, Acute; Male; NF-kappa B; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; PPAR gamma; Prostaglandin D2; Rats; Rats, Wistar; Survival Analysis; Tumor Necrosis Factor-alpha