Efficacy of various dithiol compounds in acute As2O3 poisoning in mice.
The efficacy of DL-dimercaptopropanol (British Anti-Lewisite, BAL), DL-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMSA) 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 less than or equal to 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/LD50 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 2.0. 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 of 74As(III)). Thirty minutes later the antidotes were administered i.p. (0.7 mmol/kg). From 2 to 4 h after As2O3 poisoning bile was collected from guinea pigs. Four h after As2O3 injection the content of 74As in blood, liver, kidneys, spleen, heart, lungs, brain, testes, skeletal muscle, and skin in mice and guinea pigs was measured.(ABSTRACT TRUNCATED AT 250 WORDS)
Kreppel
H
H
Walther Straub-Institut für Pharmakologie und Toxikologie der Universität München, FRG.
Reichl
F X
FX
Szinicz
L
L
Fichtl
B
B
Forth
W
W
D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D004112:Dimercaprol / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D010087:Oxides; D004113:Succimer / Q000494:pharmacology / Q000633:toxicity; D013438:Sulfhydryl Compounds / Q000494:pharmacology* / Q000633:toxicity; D014494:Unithiol / Q000494:pharmacology / Q000633:toxicity
D001152:Arsenicals; D010087:Oxides; D013438:Sulfhydryl Compounds; D004112:Dimercaprol; D014494:Unithiol; D004113:Succimer; D001151:Arsenic; D000077237:Arsenic Trioxide