Increased lead concentration in brain and potentiation of lead-induced neuronal depression in rats after combined treatment with lead and disulfiram.
The effects of disulfiram (tetraethylthiuram disulfide) on blood and brain lead levels and on lead-induced changes in growth and cerebellar Purkinje neuron excitability were assessed in adult Sprague-Dawley rats. Disulfiram is metabolized to diethyldithiocarbamate, which forms a lipophilic complex with lead, and can thereby influence the tissue distribution of lead. Pregnant rats were exposed to 0.25% lead acetate or an equimolar amount of sodium acetate in the drinking water, and these treatments were continued for 4 weeks after birth. Half of the mothers from each group were given 0.1 mmole/kg disulfiram orally twice a week until parturition, after which the treatment was continued for 4 weeks in the respective pups in the form of subcutaneous injections. Although lead exposure markedly increased blood lead levels, the increase in brain lead levels was much more modest. Disulfiram markedly increased brain lead levels while blood lead levels in this group were only slightly elevated as compared to animals receiving lead alone. In addition, the lead + disulfiram group had depressed weight gain during maturation, and Purkinje neuron firing rates were reduced. The lead alone and disulfiram alone groups were not different from controls in these respects. These data suggest that disulfiram potentiates the adverse effects of lead on growth rates and on cerebellar Purkinje neuron function by facilitating the accumulation of lead in brain tissue.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004221:Disulfiram / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D007854:Lead / Q000378:metabolism / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D007854:Lead; D004221:Disulfiram