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Efficacy of various dithiol compounds in acute As2O3 poisoning in mice

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Abstract

The efficacy ofdl-dimercaptopropanol (British Anti-Lewisite, BAL),dl-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMS A) was compared in reducing the acute As2O3 toxicity in mice. Mice were treated with a single equimolar dose of a dithiol compound (0.7 mmol/kg i.p.) 0.5 or 30 min after the s.c. injection of various doses of As2O3. Both DMPS and DMSA were significantly (p<0.05) more effective in mice treated 0.5 min after the poisoning if compared to BAL on an equimolar level. The highest potency ratio (PR) (LD50 with treatment/LD5o without treatment) was found in animals injected with DMSA (PR=8.6). The corresponding value for DMPS was 4.2, and for BAL 2.1, respectively. In animals treated 30 min after poisoning the efficacy of DMPS (PR = 2.6) was similar to the efficacy of DMSA 2.4, both being only slightly superior to BAL 2.O. DMPS and DMSA were found to be much less toxic than BAL. The LD50 of arsenic was 0.057 mmol/kg. The efficacy of BAL, DMPS, and DMSA in reducing the tissue content of arsenic following acute As2O3 poisoning was investigated in mice (n=6/group) and guinea pigs (n=3-4/group). The animals were injected s.c. with 0.043 mmol/kg As2O3 (containing a tracer dose of74As(III)). Thirty minutes later the antidotes were administered A were more effective in reducing the arsenic content of tissues than BAL. Moreover, BAL caused accumulation of the toxicant in the brain. It is concluded that the recommendation of BAL as drug of choice in acute arsenic poisoning needs to be carefully re-evaluated.

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Authors and Affiliations

  1. Walther Straub-Institut für Pharmakologie und Toxikologie der Universität München, Nussbaumstr. 26, 8000, München 2, FRG

    Helmut Kreppel, Franz -Xaver Reichl, Ladislaus Szinicz, Burckhard Fichtl & Wolfgang Forth

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  1. Helmut Kreppel
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  2. Franz -Xaver Reichl
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  3. Ladislaus Szinicz
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  4. Burckhard Fichtl
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  5. Wolfgang Forth
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Kreppel, H., Reichl, F.X., Szinicz, L. et al. Efficacy of various dithiol compounds in acute As2O3 poisoning in mice. Arch Toxicol 64, 387–392 (1990). https://doi.org/10.1007/BF01973461

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  • DOI: https://doi.org/10.1007/BF01973461

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