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|Title:||Zinc preconditioning protects against renal ischaemia reperfusion injury in a preclinical sheep large animal model.|
|Authors:||O'Kane, Dermot;Gibson, Luke;May, Clive N;du Plessis, Justin;Shulkes, Arthur;Baldwin, Graham S;Bolton, Damien;Ischia, Joseph J;Patel, Oneel|
|Affiliation:||The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia|
Australian Clinical Laboratories, Austin Health, Heidelberg, Victoria, Australia
Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Urology, Austin Health, Heidelberg, Victoria, Australia
|Citation:||Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 2018; online first: 4 July|
|Abstract:||Ischaemia-reperfusion injury (IRI) during various surgical procedures, including partial nephrectomy for kidney cancer or renal transplantation, is a major cause of acute kidney injury and chronic kidney disease. Currently there are no drugs or methods for protecting human organs, including the kidneys, against the peril of IRI. The aim of this study was therefore to investigate the reno-protective effect of Zn2+ preconditioning in a clinically relevant large animal sheep model of IRI. Further the reno-protective effectiveness of Zn2+ preconditioning was tested on normal human kidney cell lines HK-2 and HEK293. Anaesthetised sheep were subjected to uninephrectomy and 60 min of renal ischaemia followed by reperfusion. Sheep were preconditioned with intravenous injection of zinc chloride prior to occlusion. Serum creatinine and urea were measured before ischaemia and for 7 days after reperfusion. HK-2 and HEK293 cells were subjected to in vitro IRI using the oxygen- and glucose-deprivation model. Zn2+ preconditioning reduced ischaemic burden determined by creatinine and urea rise over time by ~ 70% in sheep. Zn2+ preconditioning also increased the survival of normal human kidney cells subjected to cellular stress such as hypoxia, hydrogen peroxide injury, and serum starvation. Overall, our protocol incorporating specific Zn2+ dosage, number of dosages (two), time of injection (24 and 4 h prior), mode of Zn2+ delivery (IV) and testing of efficacy in a rat model, a large preclinical sheep model of IRI and cells of human origin has laid the foundation for assessment of the benefit of Zn2+ preconditioning for human applications.|
|Subjects:||Ischaemia reperfusion injury|
|Appears in Collections:||Journal articles|
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