Effect of thiocarbamate derivatives on copper, zinc, and mercury distribution in rats and mice.

Abstract

Oral treatment of rats with tetramethylthiuram disulphide (TMTDS), 0.1% mixed in the food (corresponding to 20--30 mumol daily) for one week, increased the brain levels of endogenous copper and zinc to 120% and 170%, respectively, of the control levels. Mice injected with HgCl2 (2.5 mumol/kg) were used to study further the effect of DDC (diethyldithiocarbamate), disulfiram, TMTDS or CS2 on heavy metal distribution. The brain levels of Hg were significantly increased in mice given DDC or TMTDS. Disulfiram and CS2 increased the brain levels marginally. Pregnant rats exposed to HgCl2 (0.5 mumol/kg) were also included in the studies. Treatment with DDC (0.5 mmol/kg) immediately after the mercury injection, increased the maternal brain concentration of mercury considerably, as measured after 24 and 78 h. The kidney levels were also increased. In the foetuses, the brain and liver levels were transiently increased after treatment with diethyldithiocarbamate. The observations support the hypothesis that the neurotoxicity of diethyldithiocarbamate and other thiocarbamates may be related to changes in heavy metal metabolism.