Effect of thiuram sulphides on the uptake and distribution of nickel in pregnant and non-pregnant mice.
Oral administration of 63Ni2+ together with thiuram sulphides (tetramethylthiuram disulphide, tetraethylthiuram disulphide, tetrabutylthiuram disulphide, dipentamethylenethiuram monosulphide or dipentamethylenethiuram tetrasulphide) or sodium diethyldithiocarbamate resulted in highly increased levels of 63Ni2+ in several tissues of mice in comparison with animals given 63Ni2+ alone. Administration of these substances to pregnant animals induced increased levels of 63Ni2+ in the fetuses. The uptake of 63Ni2+ in the brains of both adults and fetuses was usually very markedly enhanced by these compounds--dipentamethylenethiuram monosulphide and tetraethylthiuram disulphide being the most efficient compounds in this respect. Determination of the chloroform/water partition coefficients for nickel in the presence of thiuram sulphides or sodium diethyldithiocarbamate showed that these compounds are able to form lipophilic complexes with the metal. A facilitated penetration through the cellular membranes of the lipophilic complexes between nickel and these substances can explain the effects on the fate of the nickel. However, the partition coefficient for nickel in presence of sodium diethyldithiocarbamate was much higher than for the thiuram sulphides, but in spite of that, the effect of sodium diethyldithiocarbamate on the disposition of 63Ni2+ in the mice was not more marked than for most of the thiuram sulphides. It has been shown that tetraethylthiuram disulphide undergoes a reductive fission in the gut to diethyldithiocarbamate, which is considered to be the active form of tetraethylthiuram disulphide. The marked effects on the disposition of the 63Ni2+ induced by the other thiuram sulphides examined in the present study suggest that a similar fission to chelating thiocarbamates will take place. However, the formation of lipophilic complexes with the original thiuram sulphides may contribute to the effects on the disposition of the 63Ni2+.
D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography; D004221:Disulfiram / Q000378:metabolism / Q000494:pharmacology; D004050:Ditiocarb / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D009532:Nickel / Q000378:metabolism* / Q000652:urine; D011247:Pregnancy; D011868:Radioisotopes; D013859:Thiocarbamates / Q000378:metabolism / Q000494:pharmacology*; D013893:Thiram / Q000494:pharmacology; D014018:Tissue Distribution
D011868:Radioisotopes; D013859:Thiocarbamates; D013893:Thiram; D009532:Nickel; D004050:Ditiocarb; D004221:Disulfiram