15-deoxy-delta 12,14-prostaglandin J2 prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2010-03, Vol.298 (3), p.G410-G418
• Main Authors: Watanabe, Katsutaka, Yokoyama, Yukihiro, Kokuryo, Toshio, Kawai, Kiyotaka, Kitagawa, Tomomi, Seki, Takashi, Nakagawa, Akifumi, Nagino, Masato
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; Bile Ducts - surgery; Bilirubin - blood; Cholangitis - blood; Cholangitis - chemically induced; Cholangitis - complications; Cholangitis - pathology; Cholangitis - prevention & control; Cholestasis, Extrahepatic - blood; Cholestasis, Extrahepatic - complications; Cholestasis, Extrahepatic - pathology; Disease Models, Animal; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Gene Expression - drug effects; Gene Expression - genetics; Hyaluronic Acid - blood; Hyaluronic Acid - metabolism; Interleukin-6 - genetics; Ligation; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - pharmacology; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver - physiopathology; Liver Circulation - physiology; Liver Failure, Acute - etiology; Liver Failure, Acute - prevention & control; Male; NF-kappa B - genetics; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type III - genetics; PPAR gamma - genetics; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - pharmacology; Prostaglandin D2 - therapeutic use; Rats; Rats, Wistar; Survival Analysis; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1522-1547
• 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 (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.