15-Deoxy-Δ12,14-prostaglandin J2 prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis

Watanabe K, Yokoyama Y, Kokuryo T, Kawai K, Kitagawa T, Seki T, Nakagawa A, Nagino M. 15-Deoxy-Delta(12,14)-prostaglandin J(2) prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis. Am J Physiol Gastrointest Liver Physiol 298: G410-G418, 2010. First published January 7, 2010; doi: 10.1152/ajpgi.00233.2009.-Acute obstructive cholangitis is a common disease with a high mortality rate. Ligands for peroxisome proliferator-activated receptor-gamma (PPAR gamma), 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.