Protective effect of EDTA preadministration on renal ischemia.

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.

• Authors: Chiara Foglieni, Alessandro Fulgenzi, Paolo Ticozzi, Fabio Pellegatta, Clara Sciorati, Daniela Belloni, Elisabetta Ferrero, Maria Elena Ferrero
• Journal: BMC nephrology (BMC Nephrol) Vol. 7 Pg. 5 (Mar 15 2006) ISSN: 1471-2369 [Electronic] England
• PMID: 16536881 (Publication Type: Journal Article)

Chemical References

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

Topics

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