Effects of Prussian Blue and N-Acetylcysteine on Thallium Toxicity in Mice

Abstract

Background: Thallium poisoning is now rare but still occurs as a result of homicide attempts. Prussian blue's efficacy in the treatment of experimental thallium poisoning has been demonstrated in animal models, and its use in humans is supported by anecdotal data. Since thallium binds sulfhydryl groups, the use of N-acetylcysteine is also considered as a potential antidote. Study Objective: To compare the efficacy of Prussian blue and N-acetylcysteine in a murine model of thallium poisoning. Methods: Female Swiss albino mice with free access to food and water were used. Two study doses of thallium, given as a subcutaneous injection of thallium acetate dissolved in sterile water, were chosen: 70 mg/kg (LD₉₀) and 85 mg/kg (>LD₁₀₀). A randomized, placebo controlled study was conducted with survival at 120 h chosen as the outcome measure. Four treatment groups were studied: control, Prussian blue, N-acetycysteine, and the combination of Prussian blue and N-acetylcysteine. Prussian blue was dissolved in water and given by oral gavage at a dose of 50 mg/kg. N-acetylcsteine was diluted in normal saline and given as intraperitoneal injection of 200 mg/kg. Sterile water by gavage and normal saline by peritoneal injection were given as control treatments whenever an active agent was not given. Survival was recorded over a 120 h study period and compared at 120 h by a Fisher's exact test.Results: At 120 h following subcutaneous injection of thallium 70mg/kg, only 10% of the control animals survived. Treatment with N-acetylcysteine or Prussian blue increased survival to 35% (p=0.13) and 50% (p=0.0014), respectively. The addition of N-acetylcysteine to Prussian blue offered no benefit over Prussian blue therapy alone. Conclusions: Prussian blue was found to decrease mortality from thallium poisoning at a dose equal to the LD₉₀ in this model, but not a dose greater than the LD₁₀₀ No role for N-acetylcysteine in the treatment of thallium poisoning was demonstrated by this study