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Determination and metabolism of dithiol chelating agents. III. Formation of oxidized metabolites of 2,3-dimercaptopropane-1-sulfonic acid in rabbit.

Authors
Maiorino-RM; Weber-GL; Aposhian-HV
Source
Drug Metab Dispos 1988 May; 16(3):455-463
NIOSHTIC No.
00184135
Abstract
A study was done to detect, isolate, and determine the structures of putative oxidized disulfide metabolites of 2,3-dimercaptopropane-1- sulfonic-acid (74613) (DMPS) in urine of treated rabbits. Male New- Zealand-White-rabbits were given unlabeled or carbon-14 labeled DMPS by intramuscular injection at 0.2 millimoles per 0.3 milliliters per kilogram. Urine was collected over the next 6 hours, alkylated, and analyzed by high pressure liquid chromatography (HPLC), atomic absorption spectroscopy (AAS), and fast atom bombardment mass spectrometry (FABMS). A mean of 3.8 percent of administered DMPS was excreted unaltered in urine over 6 hours, most of it during the first 0.5 hour. Reduction with sodium-borohydride yielded 81.8 percent of DMPS in urine, with a peak between 1 and 2 hours. Analysis of zinc and copper indicated that disulfide metabolites were not chelates of these metals. HPLC analysis suggested cyclic and acyclic disulfide metabolites which were not zinc or copper chelates. These were converted to DMPS by dithiothreitol reduction. The metabolites were identified as cyclic and acyclic polymeric disulfides by FABMS. A dimer of the parent compound comprised one acyclic disulfide. Unaltered DMPS and acyclic polymeric disulfides decreased in urine over time and cyclic polymers increased, suggesting oxidation of acyclic to cyclic products. Over 6 hours, total carbon-14 in urine was represented by 5 percent unaltered DMPS, 51 percent cyclic polymeric disulfides, 33 percent acyclic polymeric disulfides, and 11 percent unknown compounds. Spontaneous in-vitro oxidation occurred at rates different from those in-vivo but produced the corresponding disulfides. The authors conclude that both spontaneous and enzymatic oxidation reduction reactions are occurring in conversion of DMPS to disulfides.
Keywords
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Metabolic-study; Thiols; Laboratory-animals; In-vivo-studies; Urinalysis; Oxidation-reduction-reactions; Chromatographic-analysis; Mass-spectrometry; Atomic-absorption-spectrometry; In-vitro-studies
Contact
Molecular and Cellular Biology University of Arizona Biosciences West Bldg Tucson, AZ 85721
CODEN
DMDSAI
CAS No.
74-61-3
Publication Date
19880501
Document Type
Journal Article
Funding Amount
146501
Funding Type
Grant
Fiscal Year
1988
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-02185
Issue of Publication
3
ISSN
0090-9556
Priority Area
Pulmonary-system-disorders
Source Name
Drug Metabolism and Disposition
State
AZ
Performing Organization
University of Arizona, Tucson, Arizona
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