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Protective effect of zinc preconditioning against renal ischemia reperfusion
injury is dose dependent
#MMPMID28686686
Rao K
; Sethi K
; Ischia J
; Gibson L
; Galea L
; Xiao L
; Yim M
; Chang M
; Papa N
; Bolton D
; Shulkes A
; Baldwin GS
; Patel O
PLoS One
2017[]; 12
(7
): e0180028
PMID28686686
show ga
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
HIF1?, HIF2? and HIF3? 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 HIF1? and
HIF2? but not HIF3? 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.
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