Effects of perinatal treatment with lead and disulfiram on ALAD activity in blood, liver and kidney and urinary ALA excretion in rats.

Abstract

Disulfiram, which is metabolized to diethyldithiocarbamate, is known to greatly influence the tissue distribution of lead (Pb) and potentiate the toxic effect of lead in the central nervous system. Effects on delta-aminolevulinic acid dehydratase (ALAD) activity and urinary delta-aminolevulinic acid (ALA) excretion were studied in rats pre- and postnatally exposed to lead and disulfiram, singly or in combination. Pregnant rats were treated with lead (0.25% Pb in the drinking water), with disulfiram (0.1 mmol/kg orally twice a week) or with both lead and disulfiram from day 1 of pregnancy until weaning. After parturition the disulfiram was given subcutaneously directly to the offspring. ALAD activity in blood was inhibited to a similar extent in the group treated with lead alone and in the group treated with lead and disulfiram (7 and 10% of control activity, respectively). Liver and kidney ALAD activities were not affected by the combined treatment with lead and disulfiram. However, urinary excretion of ALA was increased twice as much in the group treated with lead and disulfiram as in the group treated with only lead. The haematocrits were also significantly more depressed after combined exposure to lead and disulfiram. Two weeks after cessation of exposure ALAD activity in blood was inhibited to 47% of control activity in both the lead- and the lead plus disulfiram-treated groups. At this time there was no effect due to treatment on urinary ALA excretion of haematocrit. The results indicate that disulfiram probably influences the effects of lead on ALAD activity at the site of haem synthesis in the bone marrow.2+t is