Cadmium mobilization in vivo by intraperitoneal or oral administration of monoalkyl esters of meso-2,3-dimercaptosuccinic acid in the mouse.
The relative activities of a series of nine monoalkyl esters of meso-2,3-dimercaptosuccinic acid have been examined as agents for the mobilization of cadmium from mice one week after intraperitoneal administration of cadmium chloride. Eight of these are newly synthetized; all are of the type ROOCCH(SH)CH(SH)COOH, were R = Me, MMDMS; R = C2H5, MEDMS; R = (CH2)2CH3, Mn-PDMS; R = CHMe2, Mi-PDMS; R = (CH2)3CH3, Mn-BDMS; R = CH2CHMe2, Mi-BDMS; R = (CH2)4CH3, Mn-ADMS; R = (CH2)2CHMe2, Mi-ADMS; and R = (CH2)5CH3, Mn-HDMS. All are soluble in dilute sodium bicarbonate solutions and can be administered as aqueous solutions. Cadmium mobilization data were collected on each compound using mice previously loaded with cadmium; the monoesters were administered at a level of 0.40 mmol/kg intraperitoneally daily for five days. Data on whole body cadmium mobilization indicated that the monoester with the isoamyl group was the most effective under the conditions used. The relative whole body cadmium mobilization increased with the number of carbon atoms in the alkyl group of the monoester up to C5 and then decreased for the C6 compound. Cadmium removal from the kidneys and liver was also measured. It was found that the monoisoamyl ester was the most effective in removing cadmium from both the liver and the kidneys. The monoisoamyl ester also proved to be very effective in mobilizing cadmium from both the liver and the kidneys when given orally. This is the first compound which is reported capable of mobilizing cadmium in vivo from aged deposits after oral administration.
Jones
M M
MM
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Singh
P K
PK
Gale
G R
GR
Smith
A B
AB
Atkins
L M
LM
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship; D004113:Succimer / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014018:Tissue Distribution / Q000187:drug effects
D004952:Esters; D002104:Cadmium; D004113:Succimer