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In vivo reduction of arsenate in mice and rabbits
Abstract:
In vivo reduction of AsV, has been studied in mice and rabbits by determination of arsenic metabolites in plasma and urine after administration of [74As]arsenate. The amount of AsIII in bladder urine of mice 1 hr after administration (0.04 or 0.4 mg As/kg body wt) corresponded to 0.4-2.9% of the dose. AsIII was also detected in plasma 1 hr after administration. In rabbits, catheterized in the bladder for continuous collection of urine, about 10% of the administered arsenate (0.04 mg As/kg body wt) was reduced and excreted in form of AsIII during 4 hr after administration, corresponding to about 20% of the total arsenic excreted. Arsenic excreted during the first hour was mainly in form of unmetabolized AsV and some AsIII. Thereafter the excretion of both AsIII and dimethylarsinic acid increased. The results indicated that AsV has to be reduced to AsIII before being methylated.
Insights
In vivo studies show that arsenate (AsV) must be reduced to arsenite (AsIII) before methylation occurs. This reduction and subsequent metabolism of arsenic were observed in mice and rabbits.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacokinetics
Background:
- Arsenic (As) is a metalloid with various oxidation states, including arsenate (AsV) and arsenite (AsIII).
- Understanding arsenic metabolism in vivo is crucial for assessing its toxicity and developing effective treatments.
Purpose of the Study:
- To investigate the in vivo reduction of arsenate (AsV) to arsenite (AsIII) in mammalian models.
- To determine the metabolic pathway of arsenic, specifically the order of reduction and methylation.
Main Methods:
- Administration of radiolabeled [74As]arsenate to mice and rabbits.
- Quantification of arsenic metabolites (AsV, AsIII, dimethylarsinic acid) in plasma and urine samples.
- Continuous urine collection in catheterized rabbits to track excretion patterns.
Main Results:
- Arsenite (AsIII) was detected in mouse plasma and urine within 1 hour post-administration, indicating rapid reduction of arsenate (AsV).
- In rabbits, approximately 10% of the administered arsenate was reduced and excreted as AsIII within 4 hours.
- Excretion patterns showed initial AsV and AsIII, followed by increased excretion of AsIII and dimethylarsinic acid, suggesting a sequential metabolic process.
Conclusions:
- The in vivo reduction of arsenate (AsV) to arsenite (AsIII) is a necessary prerequisite for arsenic methylation.
- These findings elucidate a critical step in the toxicokinetics and metabolic pathway of arsenic in mammals.