Dimercaptosuccinic acid and Prussian Blue in the treatment of acute thallium poisoning in rats.
BACKGROUND
Despite being banned as a pesticide, thallium still results in human and animal poisonings. Current recommended treatments include the use of the chemical Prussian Blue. Limitations in its availability may result in Prussian Blue not being obtainable in the thallium-poisoned patient. The chelator 2,3-Dimercaptosuccinic acid (DMSA) is currently FDA-approved for use in childhood lead poisoning and has been reported to be beneficial in treating other heavy metal poisonings. The objective of this study was to determine the efficacy of DMSA as a treatment for thallium poisoning by studying mortality and whole-brain concentrations in thallium poisoned rats.


METHODS
Rats were gavaged with 30 mg/kg of thallium. After 24 hours they were randomized to DMSA (n = 20) 50 mg/kg twice daily for 5 days, Prussian Blue (n = 20) 50 mg/kg twice daily for 5 days, or control (n = 30). Animals were monitored twice daily for weight loss and mortality. Animals losing greater than 20% of their starting weight were euthanized and counted as a mortality. All surviving rats at 120 hours had their brains harvested and digested and underwent subsequent thallium analysis.


RESULTS
The rate of survival in DMSA-treated animals compared to control was 45% vs. 21%, p = 0.07. Mean whole-brain thallium concentrations between DMSA and control rats were 3.4 vs. 3.0 microg/g, p = 0.06. Prussian Blue-treated rats had significantly improved survival (70% vs. 21%, p < 0.01) and lower whole-brain thallium concentrations (1.6 vs. 3.0 microg/g, p < 0.01 tissue) compared to controls.


CONCLUSIONS
DMSA failed to reduce brain thallium concentrations in rats poisoned with thallium and had an indeterminate effect on mortality while Prussian Blue significantly reduces both brain thallium concentrations and mortality.
Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. drusynia@iupui.edu
Daniel E
DE
Rusyniak
Louise W
LW
Kao
Kristine A
KA
Nanagas
Mark A
MA
Kirk
R Brent
RB
Furbee
Edward J
EJ
Brizendine
Paul E
PE
Wilmot
D000208:Acute Disease; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D005295:Ferrocyanides / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D004113:Succimer / Q000627:therapeutic use*; D016019:Survival Analysis; D013793:Thallium / Q000493:pharmacokinetics / Q000506:poisoning*; D014018:Tissue Distribution
D000931:Antidotes; D005295:Ferrocyanides; D013793:Thallium; D004113:Succimer; C000170:ferric ferrocyanide