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

Abstract

ObjectivesIschemia-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 methodsThe 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.ResultsFollowing 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.ConclusionZnCl2 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.

Ameliorative Effect of Vitamin E on Biochemical and Ultrastructural Changes in Artemether-induced Renal Toxicity in Rats

“…Glomerular capsule and vessel loops damage were also observed in nephrotic syndrome due to excessive protein loss via the damaged glomerular filtration barrier (Hall et al, 1986;Tesar et al, 1994). Moreover, Rao et al (2017) found also focal tubular dilation, flattening and attenuation of the epithelium, loss of the luminal brush border, apoptotic tubular…”

Cyclosporine-A induced nephrotoxicity in male and female rats: Is zinc a suitable protective supplement?

“…Such observation was not detected in female. The protective effect of Zn in kidney injury may be dose and gender related 34,39 , and actually the involved mechanisms is not well clear. Some of the renal function markers also were different between genders.…”

“…Until now, the role of gender or sex hormones in kidney toxicity induced by other drugs, such as cisplatin and gentamicin, have been documented [22][23][24][25][26][27][28][29][30][31][32][33] , although their mechanisms have not been completely understood. In addition, the antioxidant supplements, such as zinc (Zn), have been widely used in laboratory research to protect the kidney against injury [34][35][36][37][38][39][40][41][42] . It seems that the administration of this trace element Zn could be considered as a safe protective agent for transplant patients.…”

Does zinc possess renoprotective properties in patients under cardiac surgery?

“…[ 3 ] In these cases, evidence suggesting supplementation with antioxidant and anti-inflammatory micronutrients such as zinc can form antioxidant defense mechanisms, downregulate cytokine production, and decline cytokine concentrations and hence can reduce oxidant injury to cells and organs. [ 3 4 ] Since several renal diseases are mediated by oxidant injury, decreasing the production of reactive oxygen molecules or treating with antioxidant agents may open new avenues for research into therapeutic intervention. [ 5 ]…”

“…It can antagonize the transition of metal-catalyzed reactions and reduce the formation of hydroxyl radical from hydrogen peroxide. [ 4 ] However, its effectiveness has not been tested in a trial regarding CS-associated AKI. Berger et al .…”