title: Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats.
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.
authors.affiliation: Department of General Surgery, First Clinical College, Harbin Medical University, Harbin, China.
authors.forename: Dong-Bo
authors.initials: DB
authors.lastname: Xue
authors.forename: Wei-Hui
authors.initials: WH
authors.lastname: Zhang
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Yun
authors.forename: Chun
authors.initials: C
authors.lastname: Song
authors.forename: Biao
authors.initials: B
authors.lastname: Zheng
authors.forename: Xing-Ye
authors.initials: XY
authors.lastname: Shi
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D001152:Arsenicals; D016328:NF-kappa B; D010087:Oxides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D000681:Amylases; D000077237:Arsenic Trioxide