15-deoxy-delta 12,14-prostaglandin J2 prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis.
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.
Watanabe
Katsutaka
K
Dept. of Surgery, Nagoya Univ. Graduate School of Medicine, Showa-ku, Japan.
Yokoyama
Yukihiro
Y
Kokuryo
Toshio
T
Kawai
Kiyotaka
K
Kitagawa
Tomomi
T
Seki
Takashi
T
Nakagawa
Akifumi
A
Nagino
Masato
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001652:Bile Ducts / Q000601:surgery; D001663:Bilirubin / Q000097:blood; D002761:Cholangitis / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D001651:Cholestasis, Extrahepatic / Q000097:blood / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006820:Hyaluronic Acid / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D008026:Ligation; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008102:Liver Circulation / Q000502:physiology; D017114:Liver Failure, Acute / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin; D015230:Prostaglandin D2