Mobilization and detoxification of polonium-210 in rats by 2,3-dimercaptosuccinic acid and its derivatives.
OBJECTIVE
To reduce retention and toxicity of the alpha particle emitter polonium-210 in rats by newly developed chelating agents.


METHODS
Repeated subcutaneous chelation was conducted after intravenous injection of 210Po nitrate. For reduction of 210Po retention the treatment with vicinal dithiols meso-and rac-2,3-dimercaptosuccinic acid (DMSA), mono-i-amylmeso-2,3-dimercapto succinate (Mi-ADMS) and mono-N-(i-butyl)-meso-2,3-dimercapto succinamide (Mi-BDMA) were used. For the reduction of toxic effects of 210Po, treatment effectiveness of Mi-BDMA was compared with that of N,N'-di(2-hydroxyethyl)ethylenediamine-N,N'-biscarbodithioate (HOEtTTC, reference compound).


RESULTS
Treatment with meso-DMSA and rac-DMSA altered the main excretion route of 210Po, reduced its contents in the liver but increased its deposition in the kidneys. Treatment with Mi-ADMS or Mi-BDMA increased total excretion of 210Po, mainly via the faeces. Only Mi-BDMA decreased 210Po levels in the kidneys. The effectiveness of all chelators decreased with delay in the start of treatment. In a survival study, the lives of rats treated early with Mi-BDMA or delayed with HOEtTTC were prolonged three-fold when compared with rats receiving a lethal amount of 210Po only.


CONCLUSIONS
Of the vicinal dithiols examined, Mi-BDMA was the best mobilizing chelating agent for 210Po and it reduced 210Po toxicity when the treatment started immediately. However, the detoxification efficacy of the immediate treatment with HOEtTTC, observed in our previous study, was superior to that of the present result with Mi-BDMA.
Rencová
J
J
National Institute of Public Health, Centre of Industrial Hygiene and Occupational Diseases, Praha, Czech Republic.
Volf
V
V
Jones
M M
MM
Singh
P K
PK
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D005260:Female; D008658:Inactivation, Metabolic; D011059:Polonium / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D004113:Succimer / Q000494:pharmacology*; D014018:Tissue Distribution
D002614:Chelating Agents; D011059:Polonium; D004113:Succimer