Lead-induced inclusion bodies in rat kidney after perinatal treatment with lead and disulfiram.
The presence of inclusion bodies in renal proximal tubules was studied in rats exposed to lead and/or disulfiram (tetraethylthiuram disulfide). Pregnant rats were treated with only lead acetate (0.25% Pb in the drinking water), only disulfiram (0.1 mmol/kg p.o. twice a week) or with both lead acetate and disulfiram from day 1 of pregnancy and until the offspring were 4 weeks of age. After parturition the disulfiram was given s.c. directly to the offspring instead of to the dams. Treatment was discontinued at weaning and tissue samples from renal cortex were studied by electron microscopy. In lead-treated dams inclusions were present in nuclei of renal proximal tubule cells in the 3 segments with the highest incidence in the middle segment. Inclusions were also present in the cytoplasm. In the offspring, indirectly exposed to lead via the dams, inclusions were present in all 3 segments. No inclusions were present in control rats or in disulfiram-treated rats. Combined treatment with lead and disulfiram resulted in a marked decrease in the incidence of inclusion bodies both in the dams and in the offspring compared to in rats treated with only lead. Diethyldithiocarbamate, a major metabolite of disulfiram, forms a lipophilic complex with lead, and is known to cause pronounced effects on the tissue distribution of lead. The present investigation shows that lead inclusion bodies are formed in the offspring indirectly exposed to lead via the dams during gestation and lactation. Concurrent exposure to disulfiram reduces the incidence of inclusion bodies in renal proximal tubules, probably due to formation of a lead-dithiocarbamate complex.
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology*; D005260:Female; D002479:Inclusion Bodies / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000648:ultrastructure; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D007854:Lead / Q000032:analysis / Q000633:toxicity*; D008247:Lysosomes / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D002614:Chelating Agents; D007854:Lead; D004221:Disulfiram