Effect of a chelating drug on balance and tissue distribution of four essential metals

Numerous drugs have structures that suggest that they and/or their metabolites are chelating agents, and therefore might affect trace metal metabolism. Ethambutol, used therapeutically in the treatment of tuberculosis, is an example. The objective of this study was to determine the effects of ethambutol on tissue concentrations and balance of 4 essential trace metals: copper, iron, manganese, and zinc. Eighteen male Sprague-Dawley rats (148 +/- 7 g) were housed individually in metabolic cages. Six rats received ethambutol (400 mg/kg/day) via the drinking water. There were 2 control groups of 6 rats each, an ad-lib and a pair-fed group. Iron concentrations in kidney, liver, heart, and spleen were significantly increased in both the pair-fed and ethambutol-dosed rats, an effect related to reduced food intake. However, the total iron content of these organs was comparable to that of the ad-lib controls, suggesting retention of iron by these organs with reduced food intake during growth. Trace element balance was not affected by ethambutol administration. Ethambutol produced significant decreases in heart copper, kidney zinc, plasma zinc, and liver copper and zinc not due to the associated reduced food intake. The latter results support the hypothesis that chelating drugs may alter trace metal metabolism.