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Green Tea Polyphenols Ameliorate Pancreatic Injury in Cerulein-Induced Murine Acute Pancreatitis

Objective: Green tea polyphenols (GTPs) are naturally occurring antioxidants acting through pathways that include reactive oxygen species and nuclear factor kappa B (NF-&kgr;B). 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 &mgr;g/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-&kgr;B 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-&kgr;B inactivation. Immunostaining for P selectin and intercellular adhesion molecule 1, tumor necrosis factor &agr;, transforming growth factor &bgr;, 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-&kgr;B/IkB (inhibitor kB) proteins and oxidative stress pathways.