Protection of mice against the lethal effects of sodium arsenite?A quantitative comparison of a number of chelating agents*1

Hv, Aposhian; Ch, Tadlock; Te, Moon

doi:10.1016/0041-008x(81)90360-4

Cited by 64 publications

(16 citation statements)

References 16 publications

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“…In summary, high lipophilicity of an arsenic antidote might be unfavourable, and the limitation to the extracellular space might be the key to higher therapeutic success in acute arsenic trioxide poisoning. This hypothesis is supported by the inferior efficacy and superior lipophilicity of BAL compared to DMSA (Aposhian et al 1981(Aposhian et al , 1984Kreppel et al 1990). …”

Section: Discussionmentioning

confidence: 75%

“…They were shown also to be effective in man (BAL: Eagle and Magnuson 1946;DMSA: Lenz et al 1981;DMPS: Hruby and Donner 1987). Equimolar doses of DMPS and DMSA reduce the death rate of animals poisoned with arsenic more effectively than BAL (Tadlock and Aposhian 1980;Aposhian et al 1981Aposhian et al , 1984Aposhian 1982). Moreover, because of its lower toxicity (Kreppel et al 1990), both DMPS and DMSA can be administered at much higher doses than BAL.…”

Section: ~ H Hmentioning

confidence: 97%

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Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice

et al. 1993

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The therapeutic efficacy of six newly synthesized analogues of dimercaptosuccinic acid (DMSA) was investigated in acute arsenic trioxide poisoning in mice. Meso-2,3-di(acetylthio)succinic acid (DATSA) and meso-2,3- di(benzoylthio)succinic acid (DBTSA) are analogues of DMSA with protected thiol groups ("prodrugs"), and DMDMS, DEDMS, DnPDMS, and DiPDMS are various di-esters of DMSA with methyl, ethyl, n-propyl, and isopropyl alcohols, respectively. Thirty minutes after s.c. injection of an LD80 of arsenic trioxide (65 mumol/kg) male NMRI mice were treated with a single equimolar dose (0.7 mmol/kg) of DMSA i.p. or one of the analogues i.p. or via gastric tube (i.g.). Control animals received arsenic trioxide and saline 30 min later. The survival rate was recorded for 30 days. All of the animals treated with DMSA i.p. survived and all controls died within 2 days. Administered i.g., DATSA and DBTSA increased the survival rate to 29% and 43%, and injected i.p. to 86%. Treatment with DMDMS i.p. and i.g., and with DEDMS, DnPDMS, and DiPDMS i.g. did not reduce lethality. Given i.p., DnPDMS increased the survival rate to 72%, and DEDMS and DiPDMS to 86%, respectively. To investigate the efficacy of the DMSA analogues in reducing the tissue content of arsenic, male NMRI mice received an s.c. injection of an LD5 of arsenic trioxide containing a tracer dose of 73-As(III) (42.5 mumol/kg body wt). Thirty minutes later, saline (controls) or a single equimolar dose (0.7 mmol/kg) of DMSA i.p., or one of the analogues i.p. or i.g. was administered. The arsenic content of various organs (blood, liver, kidneys, heart, lungs, spleen, small intestine, large intestine, brain, testes, skeletal muscle, and skin) at 30 min, 2 h, 4 h, 6 h, and 8 h after the arsenic injection was measured using a gamma counter.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 75%

Section: ~ H Hmentioning

confidence: 97%

Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice

et al. 1993

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“…The basis of one type of assay is the increased excretion of the metal by metal binding agents (Cantilena & Klaassen 1982). A second assay of agents that bind metals is the prevention of the lethal effects of the particular metals by the chelating agent (Aposhian et al 1981, Hilmy 1991. In human and most of animals studied in experiments, the major route of arsenic excretion is through the kidney with only marginal elimination through feces (Vahter 1981).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic potential of meso 2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane 1-sulfonate in chronic arsenic intoxication in rats

et al. 1995

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The therapeutic efficacy of two thiol chelators, meso 2,3-dimercaptosuccinic acid (DMSA) or 2,3-dimercaptopropane sulfonate (DMPS) in treating chronic arsenic intoxication was investigated in male rats. Both the chelators were effective in promoting urinary arsenic excretion and restoring arsenic induced inhibition of blood delta-aminolevulinic acid dehydratase activity and hepatic glutathione level. Elevation of urinary delta-aminolevulinic acid excretion and arsenic concentration in blood, liver and kidneys were reduced significantly by both the chelators. Histopathological lesions induced by arsenic were also effectively reduced by the above chelators. DMSA being more effective than DMPS. The results suggest DMSA and DMPS to be effective antidotes for treating chronic arsenic toxicity in experimental animals.

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“…Equimolar levels of DMPS and DMSA reduce the lethality of animals poisoned with arsenic more effectively than BAL (Tadlock and Aposhian 1980;Aposhian et al 1981Aposhian et al , 1984Aposhian 1982). Moreover, because of its lower toxicity, both DMPS and DMSA can be administered in much higher doses than BAL, although it is not finally approved whether DMSA or DMPS is the more effective dithiol.…”

Section: Introductionmentioning

confidence: 97%

Efficacy of various dithiol compounds in acute As2O3 poisoning in mice

Kreppel¹,

Reichl²,

Szinicz³

et al. 1990

Arch Toxicol

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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)

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Protection of mice against the lethal effects of sodium arsenite?A quantitative comparison of a number of chelating agents*1

Cited by 64 publications

References 16 publications

Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice

Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice

Therapeutic potential of meso 2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane 1-sulfonate in chronic arsenic intoxication in rats

Efficacy of various dithiol compounds in acute As2O3 poisoning in mice

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