Treatment of arsenic poisoning with heavy-metal antagonists in rats (Report 2)

Abstract

Among many metal binding agents, 2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-l-propane-sulfonic acid (DMPS) have been reported as effective antagonists against toxicity of several metals including arsenic. In our study, all mice which were given arsenic trioxide (0.2 mmol As/kg, s.c.) survived by the treatment with either one of these two agents (0.4 mmol/kg, i.p.). In order to determine the effects of DMSA or DMPS on the arsenic and copper excretion in arsenic poisoning, the following experiments were conducted: In the first experiment, using 3 groups of rats, arsenic trioxide (4 mg As/kg/day, p.o.) was given to 2 groups for 3 days, one of which was simultaneously treated with DMSA (50 mg/kg/day, i.p.) for 3 days. The third group was given only DMSA. Urinary contents and tissue concentrations of arsenic and copper were determined by the method of atomic absorption spectrophotometry. The results obtained showed DMSA accelerated the urinary excretion of arsenic. Endogenous copper excretion in urine occurred in rats given only DMSA, while such an effect was not seen in the other group given either only arsenic or both arsenic and DMSA. Arsenic concentrations in liver and kidney were reduced in the DMSA group, but blood levels were not different among the test groups. In the second experiment, two groups of rats were given arsenic trioxide (5 mg As/kg/day, p.o.) for 2 days, and in one group, this was followed by DMPS (100 mg/kg/ day, i.p.) for 2 days. The third group received only DMPS (100 mg/kg/day, i.p.) for 2 days. Contrary to the results obtained in the first experiment, DMPS did not accelerate the excretion of arsenic. The simultaneous treatment with DMPS might have been necessary to obtain the same effects as those in the first experiment.