Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11601
Title: Blockade of the renin-angiotensin system improves the early stages of liver regeneration and liver function.
Authors: Koh, Shir Lin;Ager, Eleanor I;Malcontenti-Wilson, Caterina;Muralidharan, Vijayaragavan;Christophi, Christopher
Affiliation: Department of Surgery, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 23-Sep-2012
Citation: The Journal of Surgical Research 2012; 179(1): 66-71
Abstract: Partial hepatectomy is the preferred option for selected patients with colorectal cancer liver metastases (CRCLM). Sufficient liver regeneration (LR) is essential for a successful outcome in these patients. The blockade of the renin-angiotensin system (RAS) reduces the growth of several tumor types. The RAS also acts as a regulator of liver fibrosis and potentially LR. The angiotensin-converting enzyme (ACE) inhibitor, captopril, significantly inhibits the growth of CRCLM, but its effect on LR remains undefined.After 70% of partial hepatectomy, mice were randomly assigned to control or captopril-treated groups. LR was measured by liver-to-body weight ratio on days 1, 2, 4, 6, and 8. Hepatocyte proliferation, apoptosis and cell size, hepatic stellate cell (HSC) count, and sinusoidal endothelial cell density were quantified. Matrix metalloproteinase 9 (MMP-9) protein levels, liver injury markers, and RAS messenger RNA levels were also determined.At day 2, captopril increased liver-to-body weight ratio (56.5 ± 1.7 captopril versus 49.3 ± 2.4 control, P = 0.027). This was associated with increased HSC count (65.4 ± 4.8 cells per 100,000 μm(2), 48.7 ± 2.3, P = 0.007) and MMP-9 levels (0.68 ± 0.12 AU, 0.12 ± 0.04, P = 0.014). The messenger RNA levels of angiotensin-converting enzyme (P = 0.045) and angiotensin 1 receptor (P = 0.039) were reduced by captopril at day 2.Captopril enhanced early LR. This effect was associated with increased HSC numbers and MMP-9 protein, whereas hepatocyte proliferation was lower than controls. Captopril may provide a beneficial treatment option for the management of patients with CRCLM.
Internal ID Number: 23110972
URI: http://ahro.austin.org.au/austinjspui/handle/1/11601
DOI: 10.1016/j.jss.2012.09.007
URL: http://www.ncbi.nlm.nih.gov/pubmed/23110972
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.pharmacology
Animals
Apoptosis.drug effects.physiology
Captopril.pharmacology
Cell Proliferation.drug effects
Cell Size.drug effects
Hepatocytes.drug effects.pathology
Liver.drug effects.metabolism.physiology
Liver Regeneration.drug effects.physiology
Male
Matrix Metalloproteinase 9.metabolism
Mice
Mice, Inbred CBA
Models, Animal
Peptidyl-Dipeptidase A.metabolism
Receptor, Angiotensin, Type 1.metabolism
Renin-Angiotensin System.drug effects.physiology
Appears in Collections:Journal articles

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