title: Effect of IS-741 on ethionine-induced acute pancreatitis in rats: relation to pancreatic acinar cell regeneration.
abstract: BACKGROUND
  Tissue destruction arising from neutrophil infiltration of the pancreas and other organs in acute pancreatitis is supposed to be suppressed by IS-741. We studied the effect of IS-741 on acute pancreatitis induced by DL-ethionine in rats.
  
  
  METHODS
  Rats fed with a low protein diet for 11 days received daily intraperitoneal administration of DL-ethionine (20 mg/100 g) for the last 4 days of the diet. To evaluate the therapeutic effect on ethionine-induced pancreatitis, IS-741 (10 mg/kg s.c.) was administered every 8 h beginning after the second ethionine injection (IS group). An equal volume of saline was used for control rats as alternative to IS-741 (control group). The rats were killed 1, 3, 5, and 7 days after the last injection of ethionine. Blood was collected to measure concentrations of the inflammatory cytokine, interleukin-8. Histologic and biochemical examinations of the pancreas were performed. The pancreatic weight, DNA content, and protein levels were determined. The pancreas was histologically examined.
  
  
  RESULTS
  Pancreatic tissue in the control group showed marked infiltration of inflammatory cells, and acinar cell necrosis was widespread 1 day after the last injection of ethionine (day 1). The severity of acute pancreatitis was alleviated in rats treated with IS-741 (IS group). Pancreatic wet weight and DNA content in the IS group were higher than those in the control group on day 1. Pancreatic protein level per DNA in the IS group was higher than that in the control group on day 7. The plasma interleukin-8 level in the control group was higher than that in the IS group on day 5.
  
  
  CONCLUSIONS
  Therapeutic administration of IS-741 ameliorated ethionine-induced acute pancreatitis in rats, and IS-741 could be a useful drug to treat patients with severe acute pancreatitis.
authors.affiliation: Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
authors.forename: Tsunao
authors.initials: T
authors.lastname: Imamura
authors.forename: Junichi
authors.initials: J
authors.lastname: Niikawa
authors.forename: Katsuya
authors.initials: K
authors.lastname: Kitamura
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ikegami
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tanaka
authors.forename: Keiji
authors.initials: K
authors.lastname: Mitamura
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001835:Body Weight; D004195:Disease Models, Animal; D005001:Ethionine; D008297:Male; D010179:Pancreas / Q000187:drug effects*; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000963:Antimetabolites; D011725:Pyridines; C097462:IS 741; D010741:Phospholipases A; D005001:Ethionine