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  • Title: Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats.
    Author: Xue DB, Zhang WH, Yun XG, Song C, Zheng B, Shi XY, Wang HY.
    Journal: Chin Med J (Engl); 2007 Apr 20; 120(8):690-5. PubMed ID: 17517186.
    Abstract:
    BACKGROUND: It is accepted that inflammatory cytokines play a key role in the development of acute pancreatitis, so blocking the initiation of inflammatory reactions may alleviate pathological changes of acute pancreatitis. We studied the regulatory effect of arsenic trioxide (As(2)O(3)) on apoptosis and oncosis of pancreatic acinar cells in vitro and in vivo and its therapeutic effect on acute pancreatitis. METHODS: Pancreatic acinar cells were isolated by collagenase digestion method. Apoptosis and oncosis of isolated pancreatic acinar cells were detected with Hoechst 33258 + PI or Annexin V + PI double fluorescent staining. Amylase and lactate dehydrogenase release were measured. Acute pancreatitis was induced in Wistar rats by intraperitoneal injections of caerulein, and apoptosis was detected with terminal dUTP nick-end labeling method. Tumor necorsis factor alpha (TNF-alpha) mRNA, myeloperoxidase, nuclear factor-kappaB and histological grading of pancreatic damage were measured. RESULTS: There was an increased apoptosis but a decreased oncosis of pancreatic acinar cell after the treatment with As(2)O(3). The levels of lactate dehydrogenase and amylase release were markedly decreased in As(2)O(3) treated group. Myeloperoxidase content, TNF-alpha mRNA level, nuclear factor-kappaB activation and pathological score in As(2)O(3) treated group were significantly lower than in the untreated group. CONCLUSIONS: As(2)O(3) can induce apoptosis and reduce oncosis of pancreatic acinar cell, thus resulting in reduced release of endocellular enzyme of acinar cells, reduced inflammatory cell infiltration and decreased the production of inflammatory cytokines, so that the outcome of alleviated pathological changes was finally achieved.
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