title: Dimercaptan metal-binding agents influence the biotransformation of arsenite in the rabbit.
abstract: The urinary metabolites of sodium arsenite have been investigated in rabbits given sodium arsenite and water-soluble dimercaptans. Rabbits injected sc with NaAsO2 (1 mg As/kg) were given, im 1 hr later, either saline, 2,3-dimercapto-1-propanesulfonic acid (DMPS), mesodimercaptosuccinic acid (DMSA), or N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA) at 0.2 mmol/kg. Arsenic metabolites in urine collected from treated rabbits were isolated by combined anion-cation-exchange chromatography. Column fractions were acid-digested and analyzed for arsenic by direct hydride-flame atomic absorption spectrophotometry. The relative amounts of inorganic arsenic, methylarsonate, and dimethylarsinate found in 0 to 24 hr urine of rabbits given only sodium arsenite agreed closely with those reported for human subjects given arsenite po. This finding suggests that the rabbit biotransforms arsenite in a manner very similar to that of man. The urinary excretion of total arsenic between 0 and 24 hr was elevated after dimercaptan administration, but urinary excretion of total arsenic between 0 and 48 hr was unaffected. This result indicates that the action of these dimercaptans occurs early after treatment. In addition, the dimercaptans influenced differently the amounts of the arsenic metabolites excreted in the urine between 0 and 24 hr. DMPS, DMSA, or DMPA increased arsenite excretion but decreased dimethylarsinate excretion. DMPS or DMPA treatment increased methylarsonate excretion but DMSA did not. Arsenate excretion increased after DMPS or DMSA treatment but was not affected by DMPA treatment. These results suggest that the dimercaptans, in addition to increasing arsenic excretion, also influence the biotransformation of arsenite to less toxic species. The different effects on the urinary excretion of arsenic metabolites suggest that these dimercaptan metal binding agents have mechanisms of action in addition to simple chelation of inorganic arsenic.
authors.forename: R M
authors.initials: RM
authors.lastname: Maiorino
authors.forename: H V
authors.initials: HV
authors.lastname: Aposhian
mesh_terms: D000818:Animals; D001151:Arsenic / Q000378:metabolism* / Q000652:urine; D018053:Arsenites; D001711:Biotransformation / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D002852:Chromatography, Ion Exchange; D008297:Male; D010795:Phthalic Acids / Q000494:pharmacology; D011817:Rabbits; D004113:Succimer / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014494:Unithiol / Q000494:pharmacology
chemical_list: D018053:Arsenites; D002614:Chelating Agents; D010795:Phthalic Acids; D013438:Sulfhydryl Compounds; C029298:N-(2,3-dimercaptopropyl)phthalamidic acid; D014494:Unithiol; D004113:Succimer; C015001:arsenite; D001151:Arsenic