Protective effect of zinc preconditioning against renal ischemia reperfusion injury is dose dependent

Objectives Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury and chronic kidney disease. Two promising preconditioning methods for the kidney, intermittent arterial clamping (IC) and treatment with the hypoxia mimetic cobalt chloride, have never been directly compared. Furthermore, the protective efficacy of the chemically related transition metal Zn (2+) against renal IRI is unclear. Although Co (2+) ions have been shown to protect the kidney via hypoxia inducible factor (HIF), the effect of Zn 2+ ions on the induction of HIF1 alpha, HIF2 alpha and HIF3 alpha has not been investigated previously. Materials and methods The efficacy of different preconditioning techniques was assessed using a Sprague-Dawley rat model of renal IRI. Induction of HIF proteins following Zn (2+) treatment of the human kidney cell lines HK-2 (immortalized normal tubular cells) and ACHN (renal cancer) was measured using Western Blot. Results Following 40 minutes of renal ischemia in rats, cobalt preconditioning offered greater protection against renal IRI than IC as evidenced by lower peak serum creatinine and urea concentrations. ZnCl2 (10 mg/kg) significantly lowered the creatinine and urea concentrations compared to saline-treated control rats following a clinically relevant 60 minutes of ischemia. Zn (2+) induced expression of HIF1 alpha and HIF2 alpha but not HIF3 alpha in HK-2 and ACHN cells. Conclusion ZnCl2 preconditioning protects against renal IRI in a dose-dependent manner. Further studies are warranted to determine the possible mechanisms involved, and to assess the benefit of ZnCl2 preconditioning for clinical applications.