THE INFLUENCE OF CHELATION ON RADIOMANGANESE EXCRETION IN MAN AND MOUSE ' By LAURENCE

Manganese is capable of forming complex ions with many substances found naturally in the body (1). It seems reasonable to assume, therefore, that manganese injected as MnSO4 (hereafter referred to as "ionic manganese") will be complexed in the body to a varying extent shortly after administration. If the Mn is strongly chelated before it is injected, a state of competition between ligands is set up, and an estimate of the strength of the physiological binding of manganese can be gained from the degree of alteration of the natural excretory pattern of the isotope resulting from the use of the strong chelate. In order to test this assumption, manganese was administered after previous chelation with an excess of EDTA 4 (hereafter referred to as "Mn chelate"), a strong complexing agent which has been shown to have pronounced effects on the excretion of some metals (2). The excretory patterns of "ionic" and "chelated" Mn were then compared. When injected intravenously into experimental animals, manganese is rapidly removed from the circulating blood and distributed to various tissues of the body (3). The organs having the greatest capacity for manganese uptake are the liver, pancreas, and kidneys: and within the liver cell this element is concentrated to a high degree in the mitochondria (4). Excretion is almost entirely fecal, and more than half of this manganese is eliminated in the bile. Increasing the amount of manganese injected increases the rate of excretion (5, 6). An appreciable percentage also appears