Effects of the seleno-organic substance Ebselen in two different models of acute pancreatitis.
This study evaluated the effects of the seleno-organic substance Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] in two models of acute hemorrhagic and acute edematous pancreatitis. Ebselen is known to catalyze glutathione peroxidase-like reactions and to inhibit lipid peroxidation. Hemorrhagic pancreatitis was induced by feeding a choline-deficient, ethionine-supplemented (CDE) diet to mice for 66 h. Edematous pancreatitis was induced by 7-h subcutaneous injections of 50 micrograms/kg of cerulein in mice. Ebselen was given from the beginning of the CDE diet either as a subcutaneous injection of 100 mg/kg at 6-h intervals or was mixed in with the CDE diet to yield a daily dose of 100 mg/kg of Ebselen. In further experiments, Ebselen was given at various time intervals after the beginning of the CDE diet as subcutaneous injections of 100 mg/kg at 6-h intervals. In the cerulein model, Ebselen was given 5 min prior to each cerulein injection at doses from 10-500 mg/kg. Prophylactic administration of Ebselen given orally or subcutaneously significantly improved survival from 38.5% in the control group of saline-injected CDE-fed mice to 61.9 and 65.0%, respectively. Ebselen also reduced increases in serum amylase and pancreatic weight in the diet model. Therapeutic administration of Ebselen significantly increased survival only when injections were started 20 h after the beginning of the CDE diet (64%), but not when started after 40 h (44%). Similarly, increases in serum amylase and pancreatic weight due to the CDE diet were significantly reduced by Ebselen only when injections were started after 20 h but not when started after 40 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Niederau
C
C
Abteilung für Gastroenterologie, Heinrich-Heine-Universität Düsseldorf, F.R.G.
Ude
K
K
Niederau
M
M
Lüthen
R
R
Strohmeyer
G
G
Ferrell
L D
LD
Grendell
J H
JH
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001393:Azoles / Q000627:therapeutic use*; D002108:Ceruletide; D002796:Choline Deficiency; D004032:Diet; D004195:Disease Models, Animal; D005001:Ethionine / Q000008:administration & dosage; D005260:Female; D005609:Free Radicals; D054833:Isoindoles; D008297:Male; D051379:Mice; D009929:Organ Size; D016566:Organoselenium Compounds; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology; D012643:Selenium / Q000627:therapeutic use*
D001393:Azoles; D005609:Free Radicals; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D002108:Ceruletide; D000681:Amylases; D012643:Selenium; D005001:Ethionine