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dc.contributor.authorKoh, Shir Linen
dc.contributor.authorAger, Eleanor Ien
dc.contributor.authorMalcontenti-Wilson, Caterinaen
dc.contributor.authorMuralidharan, Vijayaragavanen
dc.contributor.authorChristophi, Christopheren
dc.identifier.citationThe Journal of Surgical Research 2012; 179(1): 66-71en
dc.description.abstractPartial 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.en
dc.subject.otherAngiotensin-Converting Enzyme Inhibitors.pharmacologyen
dc.subject.otherApoptosis.drug effects.physiologyen
dc.subject.otherCell Proliferation.drug effectsen
dc.subject.otherCell Size.drug effectsen
dc.subject.otherHepatocytes.drug effects.pathologyen
dc.subject.otherLiver.drug effects.metabolism.physiologyen
dc.subject.otherLiver Regeneration.drug effects.physiologyen
dc.subject.otherMatrix Metalloproteinase 9.metabolismen
dc.subject.otherMice, Inbred CBAen
dc.subject.otherModels, Animalen
dc.subject.otherPeptidyl-Dipeptidase A.metabolismen
dc.subject.otherReceptor, Angiotensin, Type 1.metabolismen
dc.subject.otherRenin-Angiotensin System.drug effects.physiologyen
dc.titleBlockade of the renin-angiotensin system improves the early stages of liver regeneration and liver function.en
dc.typeJournal Articleen
dc.identifier.journaltitleThe Journal of surgical researchen
dc.identifier.affiliationDepartment of Surgery, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australiaen
dc.type.austinJournal Articleen
item.fulltextNo Fulltext-
item.openairetypeJournal Article- (University of Melbourne)- Surgery- Surgery-
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