The Protective Effect of Zinc Against Liver Ischaemia Reperfusion Injury in a Rat Model of Global Ischaemia

Ernest Cheung; Mehrdad Nikfarjam; Louise Jackett; Damien M Bolton; Joseph Ischia; Oneel Patel

doi:10.1016/j.jceh.2019.07.006

The Protective Effect of Zinc Against Liver Ischaemia Reperfusion Injury in a Rat Model of Global Ischaemia

J Clin Exp Hepatol. 2020 May-Jun;10(3):228-235. doi: 10.1016/j.jceh.2019.07.006. Epub 2019 Jul 24.

Authors

Ernest Cheung¹, Mehrdad Nikfarjam¹, Louise Jackett², Damien M Bolton^{1

3}, Joseph Ischia^{1

3}, Oneel Patel¹

Affiliations

¹ Department of Surgery, The University of Melbourne, Victoria, Australia.
² Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia.
³ Department of Urology, Austin Health, Heidelberg, Victoria, Australia.

Abstract

Background: 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.

Aims: The aim of this study was to test the efficacy of zinc preconditioning in a rat model of global liver ischaemia.

Methods: 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.

Results: 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.

Conclusion: Zinc preconditioning reduces the overall hepatocellular damage from IRI. These results lay the foundation to assess the benefit of zinc preconditioning for clinical applications.

Keywords: ALT, Alanine Transaminase; ANOVA, Analysis of Variance; AST, Aspartate Transaminase; IRI, Ischaemia-Reperfusion Injury; injury; ischaemia; liver; reperfusion; zinc.