Effect of Oral Dithiol Compound Treatment in Acute Arsenic Trioxide Poisoning in Mice
Abstract
The efficacy of BAL (2,3-dimercaptopropanol), DMPS (2,3- dimercaptopropanesulfonate) and DMSA (2, 3-dimercaptosuccinic acid) in reducing the 76As burden was investigated in 76As-arsenite poisoned mice (n = 6/group). 30 min after a s.c. injection of 85 micron mol/kg 76As-arsenite (LD5), 0.7 mmol/ kg BAL (in peanut oil or in saline), DMPS, DMSA (both in saline) or saline (controls) were given by gastric tube. The 76As content of heart, lung, liver, kidney, spleen, small intestine, large intestine, brain, testes, muscle and skin was measured by a gamma counter 0.5, 2, 4, 6 and 8 h after the arsenic injection. DMPS was the most effective compound in decreasing organ arsenic content, followed by DMSA > BAL in saline > BAL in oil > saline. In the small and large intestine, DMPS markedly increased the arsenic content, indicating a shift from renal to fecal elimination and thereby a lower arsenic load for the kidney. Brain arsenic content was significantly increased by BAL, both in saline and in oil, but decreased by DMPS and DMSA. Comparison of the 76-arsenic elimination out of the brain following BAL treatment and the 14C-BAL content in brain of mice treated with 14C-BAL (in saline and oil) indicates that BAL is eliminated faster out of the brain than arsenic. The results suggest that BAL mediates increased arsenic penetration across the blood-brain-barrier followed by a ligand exchange of arsenic to intracellular molecules while BAL leaves the brain cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008789
Entities
People
- B. Schafer
- H. Kreppel
- L. Szincz