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Title: The Protective Effect of Zinc Against Liver Ischaemia Reperfusion Injury in a Rat Model of Global Ischaemia.
Austin Authors: Cheung, Ernest ;Nikfarjam, Mehrdad ;Jackett, Louise A ;Bolton, Damien M ;Ischia, Joseph J ;Patel, Oneel
Affiliation: Department of Surgery, The University of Melbourne, Victoria, Australia
Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia
Department of Urology, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 2020 2019-07-24
Publication information: Journal of clinical and experimental hepatology 2020; 10(3): 228-235
Abstract: Ischaemia-reperfusion injury (IRI) is a major obstacle during liver transplantation and resection surgeries for cancer, with a need for effective and safe drugs to reduce IRI. Zinc preconditioning has been shown to protect against liver IRI in a partial (70%) ischaemia model. However, its efficacy against a clinically relevant Pringle manoeuvre that results in global liver ischaemia (100%) is unknown. The aim of this study was to test the efficacy of zinc preconditioning in a rat model of global liver ischaemia. Rats were preconditioned via subcutaneous injection of 10 mg/kg of ZnCl2, 24 h and 4 h before ischaemia. Total liver ischaemia (100%) was induced by placing a clamp across the portal triad for 30 min. Liver injury was assessed by serum alanine transaminase (ALT) and aspartate transaminase (AST) levels in blood taken before ischaemia (baseline) and at 1, 2, 4, 24, 48, 72, 96 and 120 hours after ischaemia. Animals were culled after 7 days, and the harvested livers were histologically analysed. On a two-way repeated-measures analysis of variance, there was a statistically significant (p = 0.025) difference in the mean ALT levels between saline- and ZnCl2-treated groups. Specifically at 24 h after ischaemia, the ALT (341 ± 99 U/L) and AST (606 ± 78 U/L) in the zinc-treated group were significantly less than the ALT (2863 ± 828 U/L) and AST (3591 ± 948 U/L) values in the saline-treated group. Zinc significantly reduced neutrophil infiltration and necrosis compared with the saline control. Zinc preconditioning reduces the overall hepatocellular damage from IRI. These results lay the foundation to assess the benefit of zinc preconditioning for clinical applications.
DOI: 10.1016/j.jceh.2019.07.006
ORCID: 0000-0002-5145-6783
PubMed URL: 32405179
ISSN: 0973-6883
Type: Journal Article
Subjects: ALT, Alanine Transaminase
ANOVA, Analysis of Variance
AST, Aspartate Transaminase
IRI, Ischaemia-Reperfusion Injury
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