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Urinary metabolites of S[35]-BAL in the rat

A. method for the synthesis of S³⁵-BAL has been described S³⁵-sulphate was reduced to the sulphide and converted to NaS³⁵H. The NaS³⁵H was then reacted with 2:3-dibromopropanol to form S³⁵-BAL. The product was characterized by sulphydryl content, preparation of two crystalline dithiolans, sulphur analysis and chromatographic behavior.
The metabolism of S³⁵-BAL was studied in the Wistar rat. The isotopic BAL was administered by intraperitoneal injection and the S³⁵ content of the post-inject ion urine was studied. The maximum rate of S³⁵ excretion in the urine was observed in the first 6 hours after injection and was followed by a rapid decrease in S³⁵ excretion. This was true for both neutral S³⁵- sulphur and inorganic S³⁵-sulphate. The amount of neutral sulphur excreted in the urine also reached a maximum in the first 6 hours and returned to normal within 12 hours. The excretion of inorganic sulphate, however, remained abnormally high throughout the experiment. Approximately 4 - 19% of the excreted was S³⁵ in the form of inorganic sulphate while less than 0.5% was present in the ethereal sulphate. Six possible metabolic products were detected by radiochromatographic studies of the post-injection urine. These compounds were found to have the following Rf values when the chromatograms were run in a tertiary butanol-water solvent (70/35):
Compound 1 0.07 - 0.10
Compound 2 0.25 - 0.30
Compound 3 0.45 - 0.50
Compound 4 0.60 - 0.65
Compound 5 0.78 - 0.85
Compound 6 0.95 - 0.98
Compound 1 was characterized as inorganic sulphate while compound 5 was found to be a thiol compound which arose following acid hydrolysis of compound 3. Extraction studies showed only compound 2 to be extracted with ether while all but compounds 1 were found to be soluble in n-butanol. Compound 4, the major metabolite, was shown to be only slightly soluble in n-butanol and insoluble in ether. No glucuronide of BAL or its metabolites have been found in the urine and no increase in glucuronic acid excretion was observed following BAL injection. The presence of a large amount of glucose in the post-injection urine was indicated by chromatographic studies. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

Identiferoai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/40852
Date January 1953
CreatorsMatheson, Alastair Taylor
PublisherUniversity of British Columbia
Source SetsUniversity of British Columbia
LanguageEnglish
Detected LanguageEnglish
TypeText, Thesis/Dissertation
RightsFor non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.

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