Effects of chelates in chemotherapy of experimental gas-gangrene toxemia

The relative ability of the calcium chelates of calcium disodium ethylenediaminetetraacetate (EDTA) and calcium trisodium ethylenetriaminepentaacetate (DTPA) to protect mice against lethal doses of Clostridium perfringens alpha-toxin was investigated. Their protective ability was assayed by the increase in survival time of mice which had been given large doses of toxin, and by determining the median protective dose of chelate that would protect mice against toxin at a minimum lethal dose of two. In both assay procedures, intraperitoneal, intravenous, and intracutaneous injections of toxin were utilized, and with each toxin injection route the protective ability of the chelate was determined with the three routes of injection. DTPA was 10 to 20 times more effective than EDTA with both types of assay procedure and with all injection routes. DTPA may be superior to EDTA as a protective agent not only because it binds zinc to a greater extent, but also because of its greater retention in the body and its ability to gain entrance into cells. It appears that DTPA may be of value as a therapeutic agent in gas-gangrene.