An evaluation of the influence of devazepide and CCK-8S on the intact and resected rat liver.
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.
Ohlsson
B
B
Department of Surgery, University Hospital, Lund, Sweden.
Rehfeld
J F
JF
Axelson
J
J
D000818:Animals; D004247:DNA / Q000378:metabolism; D020109:Devazepide / Q000008:administration & dosage / Q000494:pharmacology*; D006498:Hepatectomy; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
C090019:8-sulfocholecystokinin octapeptide; D011506:Proteins; D011949:Receptors, Cholecystokinin; D004247:DNA; D020109:Devazepide; D012844:Sincalide