DL- and meso-dimercaptosuccinic acid: in vitro and in vivo studies with sodium arsenite.
Dimercaptosuccinic acid (DMSA) has been receiving increasing interest as an antidote for poisoning by heavy metals. Of the various isomeric forms, meso-DMSA has been studied most extensively because its preparation and purification are relatively easy. Using a variety of in vitro and in vivo procedures, we have investigated and compared DL- and meso-DMSA as antidotes for sodium arsenite. The two forms of DMSA are equally effective in preventing or reversing, in vitro, the arsenite inhibition of the activity of mouse kidney pyruvate dehydrogenase (PDH) complex, DL-DMSA, however, is superior to meso-DMSA for the in vivo reversal of PDH activity as measured in vitro. The LD50 values of DL- and meso-DMSA in the mouse were 10.84 and 13.73 mmol/kg, ip, respectively. The ED50 values of the two DMSA forms were not significantly different in mice receiving a LD99 dose of sodium arsenite. DL- and meso-DMSA were equally effective in mobilizing tissue 74As of rabbits. The activity of DMSA as an arsenic antidote appeared to be independent of its isomeric structural configuration. There did not appear to be any great advantage in using DL-DMSA instead of meso-DMSA as an arsenic antidote.
D000818:Animals; D000931:Antidotes; D001151:Arsenic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018053:Arsenites; D004305:Dose-Response Relationship, Drug; D004793:Enzyme Reactivators; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors; D011817:Rabbits; D017670:Sodium Compounds; D013237:Stereoisomerism; D004113:Succimer / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D000931:Antidotes; D018053:Arsenites; D004793:Enzyme Reactivators; D011768:Pyruvate Dehydrogenase Complex; D017670:Sodium Compounds; D013438:Sulfhydryl Compounds; C017947:sodium arsenite; D004113:Succimer; D001151:Arsenic