Decreasing 203Hg retention by intraperitoneal treatment with monoalkyl esters of meso-2,3-dimercaptosuccinic acid in rats.
The effect of nine monoalkyl esters of meso-2,3-dimercaptosuccinic acid (DMSA) on 203Hg retention after a single i.p. dose was evaluated in 6-7 week-old female albino rats. The monoesters were the monomethyl (MMDMS), monoethyl (MEDMS), mono-n-propyl (Mn-PDMS), monoisopropyl (Mi-PDMS), mono-n-butyl (Mn-BDMS), monoisobutyl (Mi-BDMS), mono-n-amyl (Mn-ADMS), monoisoamyl (Mi-ADMS) and mono-n-hexyl (Mn-HDMS). Dimercaptosuccinic acid or one of the monoesters were administered at a dose of 0.25 mmol kg-1 body wt. twice, i.e. 30 min and 24 h after 203Hg administration. The whole body (WB) radioactivity was determined on the 2nd, 4th and 6th days. The radioactivity in the carcass (C) (whole body without the gastrointestinal tract), liver (L), both kidneys (K) and brain (B) was determined 6 days after 203Hg administration. All treated animals had a significantly lower body burden of mercury than the controls. The reduction of 203Hg retention in WB and other body compartments was higher in animals treated with monoesters than in rats treated with DMSA. The relative effectiveness of the monoesters was dependent on the nature of the alkyl groups, the efficiency being higher in higher analogues. Maximum activity was attained with the C5 (Mn-ADMS, Mi-ADMS) and C6 (Mn-HDMS) esters. These chelators reduced WB, C, L, K and B mercury retention by 90, 89, 76, 93 and 80%, respectively. Iso derivatives were more efficient than the normal isomers (Mi-PDMS > Mn-PDMS; Mi-BDMS > Mn-BDMS; Mi-ADMS > Mn-ADMS).(ABSTRACT TRUNCATED AT 250 WORDS)
Kostial
K
K
Department of Mineral Metabolism, University of Zagreb, Croatia.
Blanusa
M
M
Simonović
I
I
Jones
M M
MM
Singh
P K
PK
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D004952:Esters / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008628:Mercury / Q000493:pharmacokinetics*; D008630:Mercury Poisoning / Q000188:drug therapy; D008631:Mercury Radioisotopes; D051381:Rats; D004113:Succimer / Q000494:pharmacology*
D000931:Antidotes; D004952:Esters; D008631:Mercury Radioisotopes; D004113:Succimer; D008628:Mercury