Anti-inflammatory actions of perfluorooctanoic acid and peroxisome proliferator-activated receptors (PPAR) α and γ in experimental acute pancreatitis
Introduction
Perfluorooctanoid acid (PFOA) has been shown to exert anti-inflammatory effects in carrageenan-induced skin inflammation [1]. Because agonist ligands at peroxisome proliferator-activated receptor alpha (PPAR-α) and gamma (PPAR-γ) had similar anti-inflammatory properties in this model, it was suggested that activation by PFOA of PPAR-α PPAR-γ could play a role in these anti-inflammatory effects. PPAR-α or PPAR-γ also seem to have anti-inflammatory properties in other experimental models [2], [3], [4], but their relative importance seems to depend on the model used. In experimental acute pancreatitis some data have been published for agonists of PPAR-γ [5], [6], but much less information is available for the possible effects of PPAR-α agonists. Only a recent report suggests that pancreatitis is augmented in PPAR-α knockout animals [7]. We have therefore investigated whether PFOA would have similar anti-inflammatory properties in a model of interstitial-edematous acute pancreatitis and whether such effects would be mimicked by PPAR-α and/or PPAR-γ activation.
Section snippets
Experimental procedure
Female Sprague–Dawley rats (200–250 g, Forschungsinstitut für Versuchstierzucht und -genetik, Himberg, Austria) were anesthetized with pentobarbitone sodium (40 mg/kg, i.p.). A jugular vein was cannulated for infusion of the cholecystokinin analogue cerulein (4 nmol/kg/h for 2 h); control animals received an infusion of an appropriate volume (8 ml/kg/h) of phosphate-buffered saline. PFOA (150 mg/kg), the PPAR-α agonist clofibrate (100 mg/kg) or the PPAR-γ agonist rosiglitazone (10 mg/kg) were
Inflammatory edema formation lipase activity in serum and pancreas
Four hours after the induction of acute pancreatitis by cerulein-induced exocrine hyperstimulation of the pancreas, water content of the pancreatic tissue had increased significantly by about 3–4 fold over basal values that were obtained in animals infused with phosphate-buffered saline (pbs) instead of cerulein (Table 1). Neither PFOA, nor clofibrate or rosiglitazone had any significant inhibitory effect on this edema formation. PFOA, clofibrate and rosiglitazone also had no effect on tissue
Discussion
Perfluorooctanoid acid (PFOA) is a compound that is widely used in a wide variety of industrial applications, but also has become under scrutiny because of its potential harmful effects [9]. However, PFOA also has been demonstrated to have anti-inflammatory properties. Thus, PFOA was found to be effective in reducing edema formation and thermal hyperalgesia in rat paw inflammation induced by the sulfated polysaccharide carrageenan [1]. In this model, PFOA largely attenuated the inflammatory
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