Effects of Diethyldithiocarbamate and Tetraethylthiuram Disulfide on Zinc Metabolism in Mice

Abstract

Chronic alcoholics with cirrhosis often develop symptoms of zinc deficiency. Tetraethylthiuram disulfide (TTD) is metabolized to two molecules of diethyldithiocarbamate (DDC). DDC chelates divalent metal ions, including zinc, by forming highly lipophilic neutral bis(dithiocarbamate)-metal complexes. DDC could therefore enhance the intestinal zinc uptake or increase the rate of zinc excretion. Accordingly, treatment of alcoholism with TTD could either aggravate or alleviate zinc deficiency. The present study investigated effects of DDC and TTD on intestinal zinc uptake and on the rate of zinc excretion in mice. When given as very high single oral doses, DDC and TTD increased the intestinal uptake of a single oral dose of zinc. When added to the diet and administered in lower doses, closer to those administered to humans for treatment of alcohol abuse, both compounds were without effect on the rate of excretion of the body's zinc stores. In a long-term experiment, where 65Zn was administered in the drinking water, these doses of TTD and DDC reduced the whole-body retention of 65Zn. No treatment changed the organ distribution of zinc in any of the experiments. In conclusion strong indications emerge from the present study that TTD treatment of alcoholism is more likely to reduce the intestinal zinc absorption than to enhance it as has been suggested by other authors. Thus, the widely used experimental model using single oral exposure to metal and chelator conceivably may give erroneous results, when used to predict effects of prolonged exposures.