Original CommunicationPeroxisome proliferator-activated receptor β/δ agonist GW0742 ameliorates cerulein- and taurocholate-induced acute pancreatitis in mice
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Animals
Male CD mice (20–22 g; Harlan, Milan, Italy) were housed in a controlled environment and provided with standard rodent chow and water. Animal care was in compliance with Italian regulations on protection of animals used for experimental and other scientific purposes (D.M.116192) as well as with the EEC regulations (O.J. of E.C. L 358/1 12/18/1986).
Pancreatitis induced by cerulean
Mice were randomly allocated into the following groups: (1) cerulein + vehicle group: mice were treated hourly (×5) with cerulein (50 μg/kg,
Effects of GW0742 on PPAR-β/δ expression
Western blot analysis shows that PPAR-β/δ was expressed in pancreata (Fig 1). Twenty-four hours after cerulein-induced pancreatitis, PPAR-β/δ protein expression was significantly reduced in pancreas homogenates. GW0742 treatment significantly prevented the pancreatitis-induced downregulation of PPAR-β/δ.
Effect of GW0742 treatment on AP
Cerulein-induced pancreatitis in mice was associated with significant rises in the serum levels of lipase and amylase (Fig 2, A and B, respectively). The increase in lipase and amylase was
Discussion
AP is a pathologic condition with clinical presentations varying from mild forms, in which the condition resolves after a single episode of transient abdominal symptoms, to severe and life-threatening variants, in which the onset of hemorrhagic/necrotic AP occurs early in the disease. The mortality rate for severe AP is extremely high at 30–50% and death is caused by dysfunction in additional organs other than the pancreas. The identification of clinical parameters that induce multiple organ
References (46)
- et al.
Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors
J Biol Chem
(1995) - et al.
PPARs: therapeutic targets for metabolic disease
Trends Pharmacol Sci
(2005) - et al.
PPAR delta: an uncompletely known nuclear receptor
Diabetes Metab
(2005) - et al.
Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium
J Pharmacol Methods
(1985) - et al.
Cell death pathways in pancreatitis and pancreatic cancer
Pancreatology
(2004) - et al.
Anti-inflammatory actions of perfluorooctanoic acid and peroxisome proliferator-activated receptors (PPAR) alpha and gamma in experimental acute pancreatitis
Int Immunopharmacol
(2008) - et al.
Rosiglitazone attenuates the severity of sodium taurocholate-induced acute pancreatitis and pancreatitis-associated lung injury
Arch Med Res
(2009) - et al.
PPARdelta modulates lipopolysaccharide-induced TNFalpha inflammation signaling in cultured cardiomyocytes
J Mol Cell Cardiol
(2006) - et al.
Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome
Surgery
(2000) - et al.
NF-kappaB activation is detrimental in arginine-induced acute pancreatitis
Free Radic Biol Med
(2003)
Missing pieces in the NF-kappaB puzzle
Cell
A monoclonal antibody against tumour necrosis factor-alpha improves survival in experimental multiple organ dysfunction syndrome
Cytokine
Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries
Biochem Pharmacol
Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons
Cardiovasc Diabetol
Peroxisome proliferator-activated receptor beta/delta activation improves angiotensin II-induced cardiac hypertrophy in vitro
Clin Exp Hypertens
Collagen autoimmune arthritis
Annu Rev Immunol
Type II collagen autoimmunity in animals and provocations leading to arthritis
Immunol Rev
Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat
Endocrinology
Activation of gene transcription by prostacyclin analogues is mediated by the peroxisome-proliferators-activated receptor (PPAR)
Eur J Biochem
Be fit or be sick: peroxisome proliferator-activated receptors are down the road
Mol Endocrinol
Bile-induced acute experimental pancreatitis
Scand J Gastroenterol
Acute pancreatitis
N Engl J Med
Pro- and anti-inflammatory cytokines during acute severe pancreatitis: an early and sustained response, although unpredictable of death. Parisian Study Group on Acute Pancreatitis
Crit Care Med
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Supported by a grant from the IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy.