Anti-inflammatory actions of perfluorooctanoic acid and peroxisome proliferator-activated receptors (PPAR) alpha and gamma in experimental acute pancreatitis.
Perfluorooctanoic acid (PFOA) and agonists of peroxisome proliferator-activated receptors (PPAR) alpha and gamma were investigated for potential anti-inflammatory effects in cerulein-induced acute pancreatitis in rats. PFOA significantly reduced both leukocyte accumulation and prostanoid synthesis. The PPAR-alpha agonist clofibrate had no effect on leukocyte activation but significantly inhibited prostanoid synthesis whereas the PPAR-gamma agonist rosiglitazone significantly reduced leukocyte activation but did not affect synthesis of prostaglandins in the pancreas. Neither PFOA, nor clofibrate or rosiglitazone had an effect on the formation of the inflammatory edema or elevated levels of lipase activity in the blood serum. In summary, PFOA attenuates the accumulation of activated leukocytes and reduces the synthesis of prostanoids in the pancreas during cerulein-induced acute pancreatitis. An activation of PPAR-alpha causes inhibition of prostanoid synthesis while activation of PPAR-gamma inhibits leukocyte activation.
Griesbacher
Thomas
T
Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria. thomas.griesbacher@meduni-graz.at <thomas.griesbacher@meduni-graz.at>
Pommer
Veronika
V
Schuligoi
Rufina
R
Tiran
Beate
B
Peskar
Bernhard A
BA
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002210:Caprylates / Q000494:pharmacology*; D005260:Female; D005466:Fluorocarbons / Q000494:pharmacology*; D005720:Gamma Rays; D007962:Leukocytes / Q000502:physiology; D008049:Lipase / Q000378:metabolism; D047493:PPAR alpha / Q000502:physiology*; D047495:PPAR gamma / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D002210:Caprylates; D005466:Fluorocarbons; D047493:PPAR alpha; D047495:PPAR gamma; D011453:Prostaglandins; C023036:perfluorooctanoic acid; D008049:Lipase