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

被引:23
|
作者
Babu, Benoy I. [2 ]
Malleo, Giuseppe [3 ]
Genovese, Tiziana
Mazzon, Emanuela
Di Paola, Rosanna
Crisafulli, Concetta
Caminiti, Rocco
Siriwardena, Ajith K. [2 ]
Cuzzocrea, Salvatore [1 ]
机构
[1] Univ Messina, Sch Med, Dept Clin & Expt Med & Pharmacol, Policlin Univ, I-98100 Messina, Italy
[2] Manchester Royal Infirm, Hepatobiliary Surg Unit, Manchester M13 9WL, Lancs, England
[3] GB Rossi Hosp, Dept Surg & Gastroenterol Sci, Verona, Italy
关键词
acute pancreatitis; green tea polyphenols; epigallocatechin-3-gallate; oxidative stress; cytokines; neutrophils; MOUSE MODEL; MICE; ALPHA; INHIBITION; ACTIVATION; EXPRESSION; DAMAGE; GENE;
D O I
10.1097/MPA.0b013e3181b28d11
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objective: Green tea polyphenols (GTPs) are naturally occurring antioxidants acting through pathways that include reactive oxygen species and nuclear factor kappa B (NF-kappa 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 mu g/kg, x6). 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-kappa 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-kappa B inactivation. Immunostaining for P selectin and intercellular adhesion molecule 1, tumor necrosis factor alpha, transforming growth factor beta, 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-kappa B/IkB (inhibitor kB) proteins and oxidative stress pathways.
引用
收藏
页码:954 / 967
页数:14
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