Alteration in inflammatory/apoptotic pathway and histone modifications by nordihydroguaiaretic acid prevents acute pancreatitis in swiss albino mice |
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Authors: | Ujwal Mukund Mahajan Chanchal Gupta Preshit Ravindra Wagh Pinakin Arun Karpe Kulbhushan Tikoo |
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Institution: | (1) Laboratory of Chromatin Biology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab, 160 062, India; |
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Abstract: | 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. |
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