Protective effect of EDTA preadministration on renal ischemia

BMC Nephrol. 2006 Mar 15;7:5. doi: 10.1186/1471-2369-7-5.

Abstract

Background: Chelation therapy with sodium edetate (EDTA) improved renal function and slowed the progression of renal insufficiency in patients subjected to lead intoxication. This study was performed to identify the underlying mechanism of the ability of EDTA treatment to protect kidneys from damage.

Methods: The effects of EDTA administration were studied in a rat model of acute renal failure induced by 60 minutes ischemia followed or not by 60 minutes reperfusion. Renal ischemic damage was evaluated by histological studies and by functional studies, namely serum creatinine and blood urea nitrogen levels. Treatment with EDTA was performed 30 minutes before the induction of ischemia. Polymorphonuclear cell (PMN) adhesion capability, plasmatic nitric oxide (NO) levels and endothelial NO synthase (eNOS) renal expression were studied as well as the EDTA protection from the TNFalpha-induced vascular leakage in the kidneys. Data was compared by two-way analysis of variance followed by a post hoc test.

Results: EDTA administration resulted in the preservation of both functional and histological parameters of rat kidneys. PMN obtained from peripheral blood of EDTA-treated ischemized rats, displayed a significant reduction in the expression of the adhesion molecule Mac-1 with respect to controls. NO was significantly increased by EDTA administration and eNOS expression was higher and more diffuse in kidneys of rats treated with EDTA than in the controls. Finally, EDTA administration was able to prevent in vivo the TNFalpha-induced vascular leakage in the kidneys.

Conclusion: This data provides evidence that EDTA treatment is able to protect rat kidneys from ischemic damage possibly through the stimulation of NO production.

MeSH terms

  • Acute Kidney Injury / drug therapy
  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / prevention & control
  • Animals
  • Blood Urea Nitrogen
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology
  • Cell Adhesion / physiology
  • Chelating Agents / pharmacology*
  • Chelating Agents / therapeutic use
  • Creatinine / blood
  • Disease Models, Animal
  • Disease Progression
  • Edetic Acid / pharmacology*
  • Edetic Acid / therapeutic use
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Ischemia / drug therapy
  • Ischemia / physiopathology
  • Ischemia / prevention & control*
  • Kidney / blood supply*
  • Kidney / chemistry
  • Kidney / drug effects*
  • Kidney / pathology
  • Macrophage-1 Antigen / analysis
  • Male
  • Neutrophils / chemistry
  • Neutrophils / pathology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Chelating Agents
  • Macrophage-1 Antigen
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Edetic Acid
  • Creatinine
  • Nitric Oxide Synthase Type III