Protective effect of zinc preconditioning against renal ischemia reperfusion injury is dose dependent
| Autor: | Graham S. Baldwin, Damien M Bolton, Mildred Yim, Kenny Rao, Oneel Patel, Luke Gibson, Mike Chang, Laurence A Galea, Nathan Papa, Joseph Ischia, Kapil Sethi, Arthur Shulkes, Lin Xiao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
030232 urology & nephrology lcsh:Medicine Pharmacology urologic and male genital diseases Kidney Pathology and Laboratory Medicine Vascular Medicine Biochemistry chemistry.chemical_compound 0302 clinical medicine Ischemia Basic Helix-Loop-Helix Transcription Factors Medicine and Health Sciences Urea lcsh:Science Ischemic Preconditioning Multidisciplinary Organic Compounds Acute kidney injury Cobalt Acute Kidney Injury Chemistry Zinc medicine.anatomical_structure Creatinine Reperfusion Injury Physical Sciences Anatomy Renal Ischemia Research Article Chemical Elements Cell Line 03 medical and health sciences Necrosis Signs and Symptoms Chlorides Diagnostic Medicine medicine Animals Humans Renal ischemia Dose-Response Relationship Drug urogenital system business.industry lcsh:R Organic Chemistry Chemical Compounds Biology and Life Sciences Kidneys Renal System medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit Rats 030104 developmental biology chemistry Gene Expression Regulation Zinc Compounds Ischemic preconditioning lcsh:Q business Reperfusion injury Biomarkers Kidney disease Transcription Factors |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 7, p e0180028 (2017) |
| ISSN: | 1932-6203 |
| Popis: | 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 Zn2+ against renal IRI is unclear. Although Co2+ ions have been shown to protect the kidney via hypoxia inducible factor (HIF), the effect of Zn2+ ions on the induction of HIF1α, HIF2α and HIF3α 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 Zn2+ 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. Zn2+ induced expression of HIF1α and HIF2α but not HIF3α 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. |
| Databáze: | OpenAIRE |
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