Pharmacology & Toxicology Poster Session



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the Role of Divalent Cations in the Mechanisms of EDTA Cytotoxicity

Contact Person: Michael O. Ogundele (mogundel@yahoo.com)


Ethylene diamine tetra-acetic acid (EDTA) is a metal ion-chelator that has found widespread application and role in modern medicine. It is used for the treatment of heavy-metal poisoning such as, lead, cadmium, nickel, mercury, as anticoagulant and non-specific inhibitor of certain enzymes-serum-stimulated lipoprotein lipase. It is also regarded as a toxic agent, but its margin of safety has usually been regarded as acceptable. The toxicity and limitations of EDTA in its clinical application and animal experiments has been well studied (Rosenblatt et al. 1978, Brownie et al. 1986). The mechanisms of EDTA cytotoxicity is further examined in this paper, using non-sensitized rabbit red blood cells.

The evaluation of the mechanisms by which this agent induces its toxicity might lead to a more rational laboratory use and clinical application. This fact was amply demonstrated recently in an attempt to analyze certain parameters in the human breast-milk, using EDTA as an inhibitor of in-vitro complement activation.

EDTA caused an independent hemolysis in CH50 assays of whole complement evaluation, not attributable to complement activities. It caused a significant loss of milk cells in fresh milk sample containing EDTA, compared to the same sample containing a similar volume of PBS. When used in the diluent to stop the complement activity reaction in APCh50 assay, it increased the level of final hemolysis recordable, compared to using GVB2- buffer as stopping solution. It also caused a brownish discoloration of the remaining "ghost" red blood cells as well as the reaction mixture supernatant, probably as a result of hemoglobin oxidation to methemoglobin.

Other toxic effects of EDTA has been noted on peripheral blood lymphocytes when used as an anticoagulant include increased sister-chromatid exchanges, cell-cycle kinetics, and mitotic index in human peripheral lymphocytes (Tucker and Chritsensen 1987). There is evidence that separate membrane channels exits for the transport of calcium cations, Ca2+ (also shared by Fe2+ and Zn2+) and magnesium cations (Mg2+) (Grubbs et al. 1985, Borovansky and Riley 1989). EDTA has been shown to be capable of penetrating biological membranes and tissue stroma. The possible interactions between these cations and EDTA in inducing its toxic effects need to be examined.

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Ogundele, M.O.; (1998). the Role of Divalent Cations in the Mechanisms of EDTA Cytotoxicity. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/pharmtox/ogundele0173/index.html
© 1998 Author(s) Hold Copyright