TY - JOUR
T1 - Green tea polyphenols ameliorate pancreatic injury in cerulein-induced murine acute pancreatitis
AU - Babu, Benoy I.
AU - Malleo, Giuseppe
AU - Genovese, Tiziana
AU - Mazzon, Emanuela
AU - Di Paola, Rosanna
AU - Crisafulli, Concetta
AU - Caminiti, Rocco
AU - Siriwardena, Ajith K.
AU - Cuzzocrea, Salvatore
PY - 2009/11
Y1 - 2009/11
N2 - OBJECTIVE:: Green tea polyphenols (GTPs) are naturally occurring antioxidants acting through pathways that include reactive oxygen species and nuclear factor kappa B (NF-κB). This study investigates the effect of GTPs in a cerulein-induced murine model of acute pancreatitis (AP). METHODS:: Male CD mice (median weight, 37.7 g) were divided into 4 groups: mice administered with cerulein alone, cerulein and GTP, saline alone (sham), and GTP alone. Acute pancreatitis was induced by serial intraperitoneal administration of cerulein (50 μg/kg, ×6). Green tea polyphenol was administered intraperitoneally at 25 mg/kg on the first, third, and sixth hours after pancreatitis induction.We analyzed histologic and biochemical features of AP, NF-κB pathway activity, leukocyte-mediated damage, cytokine levels, oxidative stress injury, lipid peroxidation, expression of poly-(adenosine diphosphate-ribose) synthetase, and presence of apoptosis. RESULTS:: Treatment with GTP reduced the histologic and biochemical features of AP. Western blot revealed significant NF-κB inactivation. Immunostaining for P selectin and intercellular adhesion molecule 1, tumor necrosis factor α, transforming growth factor β, vascular endothelial growth factor, nitrotirosine, poly-(adenosine diphosphate ribose) synthetase, and malondialdheide levels were significantly reduced. There was a significant down-regulation of apoptotic markers. CONCLUSIONS:: Our results demonstrated that GTP significantly ameliorated the effects of cerulein-induced AP in mice. These effects of GTP are mediated by actions at the NF-κB/IkB (inhibitor kB) proteins and oxidative stress pathways.
AB - OBJECTIVE:: Green tea polyphenols (GTPs) are naturally occurring antioxidants acting through pathways that include reactive oxygen species and nuclear factor kappa B (NF-κB). This study investigates the effect of GTPs in a cerulein-induced murine model of acute pancreatitis (AP). METHODS:: Male CD mice (median weight, 37.7 g) were divided into 4 groups: mice administered with cerulein alone, cerulein and GTP, saline alone (sham), and GTP alone. Acute pancreatitis was induced by serial intraperitoneal administration of cerulein (50 μg/kg, ×6). Green tea polyphenol was administered intraperitoneally at 25 mg/kg on the first, third, and sixth hours after pancreatitis induction.We analyzed histologic and biochemical features of AP, NF-κB pathway activity, leukocyte-mediated damage, cytokine levels, oxidative stress injury, lipid peroxidation, expression of poly-(adenosine diphosphate-ribose) synthetase, and presence of apoptosis. RESULTS:: Treatment with GTP reduced the histologic and biochemical features of AP. Western blot revealed significant NF-κB inactivation. Immunostaining for P selectin and intercellular adhesion molecule 1, tumor necrosis factor α, transforming growth factor β, vascular endothelial growth factor, nitrotirosine, poly-(adenosine diphosphate ribose) synthetase, and malondialdheide levels were significantly reduced. There was a significant down-regulation of apoptotic markers. CONCLUSIONS:: Our results demonstrated that GTP significantly ameliorated the effects of cerulein-induced AP in mice. These effects of GTP are mediated by actions at the NF-κB/IkB (inhibitor kB) proteins and oxidative stress pathways.
KW - Acute pancreatitis
KW - Cytokines
KW - Epigallocatechin-3-gallate
KW - Green tea polyphenols
KW - Neutrophils
KW - Oxidative stress
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U2 - 10.1097/MPA.0b013e3181b28d11
DO - 10.1097/MPA.0b013e3181b28d11
M3 - Article
C2 - 19672210
AN - SCOPUS:70350647312
VL - 38
SP - 954
EP - 967
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 8
ER -