Retrorsine: a kinetic study of its influence on rat liver regeneration in the portal branch ligation model.
Details
Serval ID
serval:BIB_732B4A619CD6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Retrorsine: a kinetic study of its influence on rat liver regeneration in the portal branch ligation model.
Journal
Journal of Hepatology
ISSN
0168-8278 (Print)
ISSN-L
0168-8278
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
39
Number
1
Pages
99-105
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
BACKGROUND: Retrorsine, a naturally occurring pyrrolizidine alkaloid, impairs liver regeneration after partial hepatectomy by mechanisms that are still unclear.
AIM: The aim of the study was to clarify the influence of retrorsine on cell cycle progression in the regenerating liver lobes of rats after portal branch ligation (PBL).
METHODS: Liver weight, protein and DNA contents, DNA synthesis (5'-bromodeoxyuridine (BrdU) incorporation) and cellular levels of Cyclin E, CDK-2, CDK-4 and proliferating cell nuclear antigen (PCNA) were assessed before and 24, 48, 72 and 168 h after PBL.
RESULTS: Before surgery, higher levels of cyclin E, CDK-2, CDK-4 and PCNA as well as BrdU incorporation were found in the liver of retrorsine-treated rats than in untreated rats. Liver weight gain, protein and DNA synthesis as well as induction of cell cycle related proteins were all strongly impaired by retrorsine in the regenerating lobes after PBL.
CONCLUSIONS: In conclusion, retrorsine impairs liver regeneration in the PBL model not only by an S or G2/M phase block, but also by a block located before the G1/S transition of the cell cycle.
AIM: The aim of the study was to clarify the influence of retrorsine on cell cycle progression in the regenerating liver lobes of rats after portal branch ligation (PBL).
METHODS: Liver weight, protein and DNA contents, DNA synthesis (5'-bromodeoxyuridine (BrdU) incorporation) and cellular levels of Cyclin E, CDK-2, CDK-4 and proliferating cell nuclear antigen (PCNA) were assessed before and 24, 48, 72 and 168 h after PBL.
RESULTS: Before surgery, higher levels of cyclin E, CDK-2, CDK-4 and PCNA as well as BrdU incorporation were found in the liver of retrorsine-treated rats than in untreated rats. Liver weight gain, protein and DNA synthesis as well as induction of cell cycle related proteins were all strongly impaired by retrorsine in the regenerating lobes after PBL.
CONCLUSIONS: In conclusion, retrorsine impairs liver regeneration in the PBL model not only by an S or G2/M phase block, but also by a block located before the G1/S transition of the cell cycle.
Keywords
Animals, Antineoplastic Agents, Phytogenic/pharmacology, Blotting, Western, Bromodeoxyuridine, CDC2-CDC28 Kinases/metabolism, Cyclin E/metabolism, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinases/metabolism, DNA/biosynthesis, Disease Models, Animal, Kinetics, Ligation, Liver Diseases/drug therapy, Liver Diseases/pathology, Liver Regeneration/drug effects, Male, Organ Size, Portal Vein, Proliferating Cell Nuclear Antigen/metabolism, Proto-Oncogene Proteins, Pyrrolizidine Alkaloids/pharmacology, Rats, Rats, Wistar, Weight Gain/drug effects
Pubmed
Web of science
Create date
20/10/2016 17:26
Last modification date
20/08/2019 15:31
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