Laboratory of Chromatin Biology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Mohali, Punjab 160 062, India.
Apoptosis. 2011 Nov;16(11):1138-49. doi: 10.1007/s10495-011-0643-8.
Reactive oxygen radicals, pro-inflammatory mediators and cytokines have been implicated in caerulein induced acute pancreatitis. Nordihydroguaiaretic acid (NDGA), a plant lignin, has marked anti-inflammatory properties. The present study aimed to investigate the possible protective effect of NDGA against caerulein induced pancreatitis. Acute pancreatitis was induced by intraperitoneal administration of eight doses of caerulein in male swiss albino mice. NDGA was administered after 9 h of acute pancreatitis induction. Pancreatic damage and the protective effect of NDGA were assessed by oxidative stress parameters and histopathology of pancreas. The mRNA expression of heat shock proteins (DNAJ C15 and HSPD1) was examined by real-time RT-PCR analysis. Expression of HSP 27, NF-κB, TNF-α, p-p38, Bcl-2, p-PP2A, procaspase-3, caspase-3 and histone modifications were examined by western blotting. NDGA attenuated the oxidative stress, led to increased plasma α-amylase and decreased IGF-1 in AP mice. It modulated the mRNA and protein levels of heat shock proteins and reduced the expression of NF-κB, TNF-α and p-p38. It increased the number of TUNEL positive apoptotic cells in the pancreas of AP mice. In addition, NDGA prevented the changes in modifications of histone H3 in acute pancreatitis. To best of our knowledge, this is the first report which suggests that NDGA prevents the progression of acute pancreatitis by involving alteration of histone H3 modifications and modulating the expression of genes involved in inflammatory/apoptotic cascade, which may be responsible for decreased necrosis and increased apoptosis in this model of acute pancreatitis.
活性氧自由基、促炎介质和细胞因子被认为与促蓝泌素诱导的急性胰腺炎有关。北美圣草素（NDGA），一种植物木质素，具有显著的抗炎特性。本研究旨在探讨 NDGA 对促蓝泌素诱导的胰腺炎的可能保护作用。通过腹腔内给予八剂促蓝泌素诱导雄性瑞士白化小鼠急性胰腺炎。在急性胰腺炎诱导 9 小时后给予 NDGA。通过胰腺的氧化应激参数和组织病理学评估胰腺损伤和 NDGA 的保护作用。通过实时 RT-PCR 分析检查热休克蛋白（DNAJ C15 和 HSPD1）的 mRNA 表达。通过 Western 印迹检查 HSP27、NF-κB、TNF-α、p-p38、Bcl-2、p-PP2A、procaspase-3、caspase-3 和组蛋白修饰的表达。NDGA 减轻了氧化应激，导致 AP 小鼠的血浆 α-淀粉酶升高和 IGF-1 降低。它调节热休克蛋白的 mRNA 和蛋白水平，并降低 NF-κB、TNF-α 和 p-p38 的表达。它增加了 AP 小鼠胰腺中 TUNEL 阳性凋亡细胞的数量。此外，NDGA 防止了急性胰腺炎中组蛋白 H3 修饰的变化。据我们所知，这是第一项表明 NDGA 通过改变组蛋白 H3 修饰并调节参与炎症/凋亡级联的基因表达来预防急性胰腺炎进展的报告，这可能是该急性胰腺炎模型中坏死减少和凋亡增加的原因。
