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An evaluation of the influence of devazepide and CCK-8S on the intact and resected rat liver

Ohlsson, Bodil LU ; Rehfeld, J F and Axelson, Jan LU (1998) In European Surgical Research 30(6). p.378-384
Abstract
BACKGROUND: Recently, it has been shown that infusion of the CCK-A receptor antagonist devazepide induced proliferation of hepatocytes and bile duct epithelium in the rat liver. The aim of this study was to further evaluate the influence of devazepide and sulfated cholecystokinin-8 (CCK-8S) on the intact rat liver and rat liver after resection. METHODS: In the first experiment, either saline or devazepide was injected subcutaneously twice daily to rats for 18 and 36 h and 3 and 7 days. In the second experiment, a 70% liver resection was followed by infusion of either DMSO, devazepide, saline or CCK-8S for 2 or 7 days. Prior to sacrifice, all rats received 1 mCi/kg of tritiated thymidine intraperitoneally. The liver was excised and the... (More)
BACKGROUND: Recently, it has been shown that infusion of the CCK-A receptor antagonist devazepide induced proliferation of hepatocytes and bile duct epithelium in the rat liver. The aim of this study was to further evaluate the influence of devazepide and sulfated cholecystokinin-8 (CCK-8S) on the intact rat liver and rat liver after resection. METHODS: In the first experiment, either saline or devazepide was injected subcutaneously twice daily to rats for 18 and 36 h and 3 and 7 days. In the second experiment, a 70% liver resection was followed by infusion of either DMSO, devazepide, saline or CCK-8S for 2 or 7 days. Prior to sacrifice, all rats received 1 mCi/kg of tritiated thymidine intraperitoneally. The liver was excised and the contents of protein, DNA and water and incorporation of tritiated thymidine were measured. RESULTS: Intermittent injections of devazepide increased the liver protein content after 36 h, followed by a decrease after 7 days. The weight, DNA content or cell proliferation was not affected. Two days after liver resection hyperCCKemia was evoked, which was less prominent after 7 days. Devazepide lowered the plasma concentration of CCK, while the infusion of CCK-8S resulted in extremely high concentrations at both time points. The DNA synthesis measured by thymidine incorporation was increased by devazepide on day 2, whereas the weight or protein and DNA contents of the liver were not influenced. CCK-8S infusion decreased the body and liver weight throughout the study, and the protein and DNA contents after 7 days. CONCLUSIONS: Intermittent devazepide treatment did not affect the intact liver. Devazepide increased the DNA synthesis 2 days after liver resection but was without other influences on the liver regeneration. CCK-8S induced decreased body weight with ensuing negative effects on the liver regeneration. Neither devazepide nor CCK seem to be of any therapeutic use after liver resection or liver failure. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Liver, Liver resection, CCK, Devazepide, Trophic effects
in
European Surgical Research
volume
30
issue
6
pages
378 - 384
publisher
Karger
external identifiers
  • pmid:9838229
  • scopus:0031774751
ISSN
0014-312X
DOI
10.1159/000008602
language
English
LU publication?
yes
id
fcf08d71-95b8-4ba6-9aea-0028dd6cea2c (old id 1113119)
date added to LUP
2008-07-14 12:06:20
date last changed
2017-01-01 04:36:22
@article{fcf08d71-95b8-4ba6-9aea-0028dd6cea2c,
  abstract     = {BACKGROUND: Recently, it has been shown that infusion of the CCK-A receptor antagonist devazepide induced proliferation of hepatocytes and bile duct epithelium in the rat liver. The aim of this study was to further evaluate the influence of devazepide and sulfated cholecystokinin-8 (CCK-8S) on the intact rat liver and rat liver after resection. METHODS: In the first experiment, either saline or devazepide was injected subcutaneously twice daily to rats for 18 and 36 h and 3 and 7 days. In the second experiment, a 70% liver resection was followed by infusion of either DMSO, devazepide, saline or CCK-8S for 2 or 7 days. Prior to sacrifice, all rats received 1 mCi/kg of tritiated thymidine intraperitoneally. The liver was excised and the contents of protein, DNA and water and incorporation of tritiated thymidine were measured. RESULTS: Intermittent injections of devazepide increased the liver protein content after 36 h, followed by a decrease after 7 days. The weight, DNA content or cell proliferation was not affected. Two days after liver resection hyperCCKemia was evoked, which was less prominent after 7 days. Devazepide lowered the plasma concentration of CCK, while the infusion of CCK-8S resulted in extremely high concentrations at both time points. The DNA synthesis measured by thymidine incorporation was increased by devazepide on day 2, whereas the weight or protein and DNA contents of the liver were not influenced. CCK-8S infusion decreased the body and liver weight throughout the study, and the protein and DNA contents after 7 days. CONCLUSIONS: Intermittent devazepide treatment did not affect the intact liver. Devazepide increased the DNA synthesis 2 days after liver resection but was without other influences on the liver regeneration. CCK-8S induced decreased body weight with ensuing negative effects on the liver regeneration. Neither devazepide nor CCK seem to be of any therapeutic use after liver resection or liver failure.},
  author       = {Ohlsson, Bodil and Rehfeld, J F and Axelson, Jan},
  issn         = {0014-312X},
  keyword      = {Liver,Liver resection,CCK,Devazepide,Trophic effects},
  language     = {eng},
  number       = {6},
  pages        = {378--384},
  publisher    = {Karger},
  series       = {European Surgical Research},
  title        = {An evaluation of the influence of devazepide and CCK-8S on the intact and resected rat liver},
  url          = {http://dx.doi.org/10.1159/000008602},
  volume       = {30},
  year         = {1998},
}