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Title: Why is it worth testing the ability of zinc to protect against ischaemia reperfusion injury for human application.
Authors: Ischia, Joseph J;Bolton, Damien M;Patel, Oneel
Affiliation: Department of Surgery, The University of Melbourne, Austin Health, Studley Rd., Heidelberg, Victoria 3084, Australia. and Department of Urology, Austin Health, Heidelberg, Victoria, Australia
Department of Surgery, The University of Melbourne, Austin Health, Studley Rd., Heidelberg, Victoria 3084, Australia
Issue Date: 17-Jun-2019
EDate: 2019-06-17
Citation: Metallomics : integrated biometal science 2019; online first: 17 June
Abstract: Ischaemia (interruption in the blood/oxygen supply) and subsequent damage induced by reperfusion (restoration of blood/oxygen supply) ultimately leads to cell death, tissue injury and permanent organ dysfunction. The impact of ischaemia reperfusion injury (IRI) is not limited to heart attack and stroke but can be extended to patients undergoing surgeries such as partial nephrectomy for renal cancer, liver resection for colorectal cancer liver metastasis, cardiopulmonary bypass, and organ transplantation. Unfortunately, there are no drugs that can protect organs against the inevitable peril of IRI. Recent data show that a protocol incorporating specific Zn formulation, dosage, number of dosages, time of injection, and mode of Zn delivery (intravenous) and testing of efficacy in a large preclinical sheep model of IRI strongly supports human trials of Zn preconditioning. No doubt, scepticism still exists among funding bodies and research fraternity on whether Zn, a naturally occurring metal, will work where everything else has failed. Therefore, in this article, we review the conflicting evidence on the promoter and protector role of Zn in the case of IRI and highlight factors that may help explain the contradictory evidence. Finally, we review the literature related to the knowledge of Zn's mechanism of action on ROS generation, apoptosis, HIF activation, inflammation, and signal transduction pathways, which highlight Zn's likelihood of success compared to various other interventions targeting IRI.
DOI: 10.1039/c9mt00079h
ORCID: 0000-0001-5628-7205
PubMed URL: 31204765
Type: Journal Article
Appears in Collections:Journal articles

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