Peroxisome proliferator-activated receptor gamma agonist reduces the severity of post-ERCP pancreatitis in rats.
OBJECTIVE
To determine the effects of prophylactic peroxi-some proliferator-activated receptor (PPARgamma) agonist administration in an experimental model of post-endoscopic retrograde cholangiopancreatography (post-ERCP) acute pancreatitis.


METHODS
Post-ERCP pancreatitis was induced in male Wistar rats by infusion of contrast medium into the pancreatic duct. In additional group, rosiglitazone, a PPARgamma agonist, was administered 1 h before infusion of contrast medium. Plasma and pancreas samples were obtained 6 h after the infusion.


RESULTS
Infusion of contrast medium into the pan-creatic duct resulted in an inflammatory process characterized by increased lipase levels in plasma, and edema and myeloperoxidase activity (MPO) in pancreas. This result correlated with the activation of nuclear factor kappaB (NFkappaB) and the inducible NO synthase (iNOS) expression in pancreatic cells. Rosiglitazone reduced the increase in lipase and the level of edema and the increase in myeloperoxidase as well as the activation of NFkappaB and iNOS expression.


CONCLUSIONS
A single oral dose of rosiglitazone, given 1 h before post-ERCP pancreatitis induction is effective in reducing the severity of the subsequent inflammatory process. The protective effect of rosiglitazone was associated with NFkappaB inhibition and the blockage of leukocyte infiltration in pancreas.
Folch-Puy
Emma
E
Department of Experimental Pathology, IIBB-CSIC, IDIBAPS, Barcelona, Spain.
Granell
Susana
S
Iovanna
Juan L
JL
Barthet
Marc
M
Closa
Daniel
D
D000208:Acute Disease; D000818:Animals; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects*; D003287:Contrast Media / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008049:Lipase / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy*; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D012720:Severity of Illness Index; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
D003287:Contrast Media; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D008049:Lipase