Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis.
OBJECTIVE
To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-gamma (PPARgamma) ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas.


METHODS
AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1beta (IL-1beta) and IL-10 were determined. Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1beta and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein.


RESULTS
Pioglitazone administered (10-100 mg/kg i.g.) 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1beta and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment.


CONCLUSIONS
Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1beta and to the overexpression of HSP70. PPARgamma ligands could represent a new therapeutic option in the treatment of AP.
Konturek
Peter C
PC
First Department of Medicine, University Erlangen-Nurnberg, Erlangen, Germany. peter.konturek@med1.imed.uni-erlangen.de
Dembinski
Artur
A
Warzecha
Zygmunt
Z
Burnat
Grzegorz
G
Ceranowicz
Piotr
P
Hahn
Eckhart G
EG
Dembinski
Marcin
M
Tomaszewska
Romana
R
Konturek
Stanislaw J
SJ
D000818:Animals; D002108:Ceruletide / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood; D008049:Lipase / Q000097:blood; D008297:Male; D047495:PPAR gamma / Q000378:metabolism*; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010195:Pancreatitis / Q000139:chemically induced* / Q000473:pathology; D000077205:Pioglitazone; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D045162:Thiazolidinediones / Q000378:metabolism / Q000494:pharmacology
D018840:HSP70 Heat-Shock Proteins; D007375:Interleukin-1; D047495:PPAR gamma; D020011:Protective Agents; D045162:Thiazolidinediones; D016753:Interleukin-10; D002108:Ceruletide; D004247:DNA; D008049:Lipase; D000077205:Pioglitazone