Document Type
Thesis
Date of Award
5-31-1984
Degree Name
Master of Science in Environmental Engineering - (M.S.)
Department
Civil and Environmental Engineering
First Advisor
John D. Bogdan
Second Advisor
Richard B. Trattner
Abstract
Numerous drugs have structures which suggest that they and/or their metabolites are likely to be chelating agents and therefore might affect trace element metabolism. For some drugs, their therapeutic activity or side effects may be due to this chelating potential. Ethambutol, used in the treatment of tuberculosis, is an example. There is also evidence that other drugs, such as alpha-methyldopa, may possess this potential; although its primary therapeutic action occurs via mechanisms other than chelation. The objective of this thesis was to determine the effects of ethambutol and alpha-methyldopa on tissue metal concentrations and balance of four essential trace metals: copper, iron, manganese, and zinc.
Two individual sub-chronic studies were separately conducted. In both studies eighteen male Sprague-Dawley rats (Ethambutol 148 ± 7g, Alpha-Methyldopa 142 ± 8g) were housed individually in metabolic cages. In the ethambutol study, six rats received ethambutol (400 mg/kg/da) via the drinking water. There were two control groups of 6 rats each, an ad-lib and a pair-fed group. Iron concentrations in the 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. Ethambutol produced significant decreases in heart copper, kidney zinc, and liver copper and zinc not due to the associated reduced food.
In the second study conducted with alpha-methyldopa, rats were also divided into 3 groups of 6 rats each. One group received a dose of 300 mg/kg/da, another 600 mg/kg/da and the final group was pair-fed to the high dose rats. Alpha-methyldopa produced a significant decrease in zinc concentration in the lungs, heart and spleen. However, the variability of these results was high. In both studies, trace element balance was not affected by drug administration.
The results of this thesis support the hypothesis that some chelating drugs may alter trace element metabolism.
Recommended Citation
Solecki, Thomas J., "Effects of two chelating drugs on trace element metabolism in the rat" (1984). Theses. 3619.
https://digitalcommons.njit.edu/theses/3619
