New Insights into EDTA In Vitro Effects on Endothelial Cells and on In Vivo Labeled EDTA Biodistribution

Abstract

EDTA chelation therapy has recently been proposed for the treatment of patients affected by neurodegenerative (ND) or cardiovascular (CVD) diseases due to its efficacy in removing toxic metals that affect the functions of neurons and endothelial cells. We examined the effects of EDTA in modulating human umbilical vein endothelial cell (HUVEC) activation induced by tumor necrosis factor alpha (TNFα). Moreover, we studied the biodistribution of technetium [99 mTc] EDTA injected intravenously into healthy adult rats. Our results show that EDTA treatment reverses the HUVEC activation induced by TNFα, as highlighted by normal tubulin distribution, in keeping with a well spread, quiescent endothelial phenotype. In addition, the biodistribution of labeled EDTA reaches the central nervous system (CNS), as assessed by scintigraphy (5853.6 cpm/pixel measured at 1 hour following intravenous labeled EDTA injection) and autopsy data (3.67% at 3 hours following labeled EDTA intravenous injection). Such evidence highlights new insights into the usefulness of EDTA chelation therapy in the treatment of ND and CVD.