Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-gamma, reduces acute pancreatitis induced by cerulein.
OBJECTIVE
In the present study, we investigated the effects of rosiglitazone (10 mg/kg, i.p.), a PPAR-gamma agonist, on the development of acute pancreatitis.


METHODS
Intraperitoneal injection of cerulein in mice induced an acute pancreatitis characterized by edema, neutrophil infiltration elevated serum levels of amylase and lipase. This experimental model was performed to test the anti-inflammatory activity of rosiglitazone. SETTING. University research laboratory.


METHODS
Male CD mice (20-22 g) were allocated into four groups (n=10 for each group): (a) Cerulein+vehicle group. Mice were treated hourly (x 5) with cerulein (50 microg/kg, in saline solution, i.p.); (b) Rosiglitazone group (same as the Cerulein+vehicle group but were administered rosiglitazone, 10 mg/kg bolus, 30 min prior to cerulein); (c) Sham+saline group. Mice were treated with saline instead of cerulein; (d) Sham+Rosiglitazone. Identical to Rosiglitazone group except that the saline was administered instead of cerulein. Mice were killed at 6 h after the induction of pancreatitis. Blood samples, pancreas, and lungs were collected.


RESULTS
Infiltration of pancreatic and lung tissue with neutrophils was associated with enhanced lipid peroxidation. Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine and for ICAM-1 in the pancreas of cerulein-treated mice. In contrast, the degree of (a) pancreatic inflammation and tissue injury, (b) upregulation/formation of ICAM-1 and nitrotyrosine, and (c) neutrophils infiltration was markedly reduced in pancreatic tissue obtained from rosiglitazone-treated mice.


CONCLUSIONS
These findings support the view that rosiglitazone and other potent PPAR-gamma agonists may be useful in the therapy of acute pancreatitis.
Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, 98123 Messina, Italy. salvator@unime.it
Salvatore
S
Cuzzocrea
Barbara
B
Pisano
Laura
L
Dugo
Angela
A
Ianaro
Domenico
D
Britti
Nimesh S A
NS
Patel
Rosanna
R
Di Paola
Tiziana
T
Genovese
Massimo
M
Di Rosa
Achille P
AP
Caputi
Christoph
C
Thiemermann
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002108:Ceruletide / Q000633:toxicity*; D008049:Lipase / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D010195:Pancreatitis / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014157:Transcription Factors / Q000819:agonists*
D015815:Cell Adhesion Molecules; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D002108:Ceruletide; D008049:Lipase; D000681:Amylases