Journal Article

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

Chang, Mike, Shulkes, Arthur, Patel, Oneel, Yim, Mildred, Gibson, Luke, Bolton, Damien, Galea, Laurence, Papa, Nathan, Sethi, Kapil, Baldwin, Graham S., Ischia, Joseph, Xiao, Lin, Rao, Kenny

2017

Overview

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. 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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acute Kidney Injury - drug therapy / Acute Kidney Injury - physiopathology / Animals / Basic Helix-Loop-Helix Transcription Factors - biosynthesis / Basic Helix-Loop-Helix Transcription Factors - blood / Biology and Life Sciences / Biotechnology / Cancer / Carbon dioxide / Care and treatment / Cell Line / Chlorides / Chlorides - administration & dosage / Chronic kidney failure / Clamping / Cobalt / Cobalt - administration & dosage / Cobalt chloride / Complications and side effects / Creatinine / Creatinine - blood / Dose-Response Relationship, Drug / Gene expression / Gene Expression Regulation - drug effects / Humans / Hypoxia / Hypoxia-inducible factor 1 / Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis / Hypoxia-Inducible Factor 1, alpha Subunit - blood / Injuries / Ions / Ischemia / Ischemic Preconditioning - methods / Kidney - drug effects / Kidney - physiopathology / Kidney cancer / Kidney transplantation / Kidneys / Laparoscopy / Medicine and Health Sciences / Physical Sciences / Preconditioning / Proteins / Rats / Reperfusion / Reperfusion injury / Reperfusion Injury - blood / Reperfusion Injury - drug therapy / Reperfusion Injury - physiopathology / Risk factors / Rodents / Surgery / Therapeutic applications / Transcription Factors - biosynthesis / Transcription Factors - blood / Urea / Urea - blood / Urology / Zinc / Zinc (Nutrient) / Zinc Compounds - administration & dosage