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Chelating agents in the treatment of acute vanadyl sulphate intoxication in mice
J L Domingo1, M Gomez, J M Llobet
1Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona, Spain.
Abstract:
Eighteen chelating or reducing agents were tested to determine their relative efficacy as antagonists in acute intramuscular vanadyl sulphate intoxication in mice. The chelating or reducing agents were administered intraperitoneally to male Swiss mice at doses equal to one-fourth of their respective LD50. Therapeutic effectiveness (TEF) was calculated. In a subsequent experiment, the effect of EDTA, glutathione, DFOA, ascorbic acid, succinic acid, monosodium phosphate, Tiron, DTPA, and 2-mercaptosuccinic acid on the excretion, and distribution of vanadium was determined. Of the compounds examined, Tiron followed by ascorbic acid, and 2-mercaptosuccinic acid were effective in increasing the urinary excretion of vanadium. Tiron, and 2-mercaptosuccinic acid were also effective in reducing the concentration of vanadium found in kidney, the main target organ of vanadium accumulation. Tiron appears to be the most effective agent of those tested in the prevention of acute vanadium (IV) intoxication in mice.
Insights
Tiron, ascorbic acid, and 2-mercaptosuccinic acid effectively increased vanadium excretion and reduced kidney vanadium levels in mice. Tiron demonstrated the highest efficacy in preventing acute vanadium intoxication.
Area of Science:
- Toxicology
- Pharmacology
- Environmental Health
Background:
- Vanadium compounds, particularly vanadyl sulfate, pose toxicity risks.
- Acute vanadium intoxication can lead to significant organ damage, especially in the kidneys.
- Antidotal strategies are crucial for managing vanadium poisoning.
Purpose of the Study:
- To evaluate the efficacy of various chelating and reducing agents as antagonists against acute vanadyl sulfate intoxication in mice.
- To determine the impact of selected agents on vanadium excretion and tissue distribution.
Main Methods:
- Eighteen chelating/reducing agents were tested for therapeutic effectiveness (TEF) against vanadyl sulfate intoxication in mice.
- Selected agents (EDTA, glutathione, DFOA, ascorbic acid, succinic acid, monosodium phosphate, Tiron, DTPA, 2-mercaptosuccinic acid) were assessed for their effects on vanadium excretion and distribution.
- Mice were administered agents intraperitoneally at 1/4 of their LD50.
Main Results:
- Tiron, ascorbic acid, and 2-mercaptosuccinic acid significantly increased urinary vanadium excretion.
- Tiron and 2-mercaptosuccinic acid reduced vanadium concentration in the kidneys, a primary target organ.
- Tiron emerged as the most effective agent in preventing acute vanadium (IV) intoxication among those tested.
Conclusions:
- Tiron, ascorbic acid, and 2-mercaptosuccinic acid show promise as therapeutic agents for vanadium intoxication.
- Tiron exhibits superior efficacy in mitigating acute vanadium toxicity and reducing vanadium accumulation in target organs.
- Further research into Tiron's mechanism and clinical application for vanadium poisoning is warranted.