A comparative study of the influence of vicinal dithiols and a dithiocarbamate on the biliary excretion of cadmium in rat.
The effect of two vicinal dithiols, 2,3-dimercaptopropan-1-ol (BAL) and N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA), and a dithiocarbamate, sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate (MeOBGDTC), on the biliary excretion of cadmium was examined in rats. Tissue cadmium levels were also determined following the measurements of biliary excretion of cadmium. At 30 min after the injection of CdCl2.2.5H2O (1 mg/kg, iv) each rat was given 400 mumol/kg ip of one of the compounds, BAL, DMPA or MeOBGDTC. While all the compounds increased the biliary excretion of cadmium, the most effective was MeOBGDTC, whose administration resulted in a 580% increase in biliary cadmium content. The effectiveness of the MeOBGDTC may be due to the presence of both nonpolar and nonionizing polar groups attached to nitrogen. MeOBGDTC was able to mobilize cadmium to the bile even after the occurrence of the synthesis of metallothionein and the incorporation of the cadmium into it. An attempt was also made to determine the chemical nature of the Cd-MeOBGDTC complex present in the bile by comparing a newly synthesized authentic sample of Cd(MeOBGDTC)2 complex with the hot dioxane extract of the freeze-dried bile samples using thin-layer chromatography and proton NMR. The results suggested that cadmium excreted in the bile in part, is complexed to MeOBGDTC and glutathione.
Jones
M M
MM
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Cherian
M G
MG
Singh
P K
PK
Basinger
M A
MA
Jones
S G
SG
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004112:Dimercaprol / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010795:Phthalic Acids / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds; D013859:Thiocarbamates / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
D002614:Chelating Agents; D010795:Phthalic Acids; D013438:Sulfhydryl Compounds; D013859:Thiocarbamates; D002104:Cadmium; D004112:Dimercaprol; C060427:N-(4-methoxybenzyl)glucamine dithiocarbamate; C029298:N-(2,3-dimercaptopropyl)phthalamidic acid; D013012:Sorbitol