title: Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats.
abstract: BACKGROUND
  Nontoxic heat shock protein (HSP) inducer compounds open up promising therapeutic possibilities by activating one of the natural and highly conserved defense mechanisms of the organism.
  
  
  OBJECTIVE
  In the present experiments, we examined the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats.
  
  
  METHODS
  Male Wistar rats weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220 was administered orally, followed by 75 microg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The animals in group slashed circleB received physiological saline orally instead of BRX-220, but otherwise the protocol was the same as in group B. The rats were exsanguinated through the abdominal aorta 12 h after the last administration of CCK. We determined the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic weight/body weight ratio, the DNA and total protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree of lipid peroxidation, protein oxidation, and the reduced glutathione level. Histopathological investigation of the pancreas was also performed in all cases.
  
  
  RESULTS
  Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 were significantly increased in the animals treated with BRX-220. In group B, the pancreatic total protein content and the amylase and trypsinogen activities were significantly higher vs. group slashed circleB. The plasma trypsinogen activation peptide concentration, and the pancreatic lipid peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase were significantly decreased in group B vs. group slashed circleB, whereas the glutathione peroxidase activity was increased. The morphological damage in group B was significantly lower than that in group slashed circleB.
  
  
  CONCLUSIONS
  The HSP coinducer BRX-220, administered for 5 d, has a protective effect against CCK-induced acute pancreatitis.
authors.affiliation: First Department of Medicine, University of Szeged, Hungary. raz@in1st.szote.u-szeged.hu
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: Béla
authors.initials: B
authors.lastname: Iványi
authors.forename: Ilona
authors.initials: I
authors.lastname: Varga
authors.forename: Imre
authors.initials: I
authors.lastname: Boros
authors.forename: Andrea
authors.initials: A
authors.lastname: Jednákovits
authors.forename: Ilona
authors.initials: I
authors.lastname: Németh
authors.forename: János
authors.initials: J
authors.lastname: Lonovics
authors.forename: Tamás
authors.initials: T
authors.lastname: Takács
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D018834:Chaperonin 60 / Q000096:biosynthesis*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006898:Hydroxylamines / Q000494:pharmacology*; D008049:Lipase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism
chemical_list: D018834:Chaperonin 60; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006898:Hydroxylamines; D014362:Trypsinogen; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008049:Lipase; D000681:Amylases; C486387:arimoclomol; D005978:Glutathione; D012844:Sincalide