Free-ranging Rats Research Articles

Studies on heparin degradation—II: The metabolic fate of the potassium salts of ([ 35S] sulphoamino)-heparin, ([ 35S] sulphoamino)-chitosan, 2-deoxy-2-[ 35S] Sulphoamino- d-glucose and [ 35S] sulphoamino- l-serine in the rat

The metabolic fate of the potassium salts of ([ 35S] sulphoamino)-heparin, ([ 35S] sulphoamino)-chitosan, 2-deoxy-2-[ 35S] sulphoamino- d-glucose and [ 35S] sulphoamino- l-serine has been investigated following administration to free-ranging rats. The intravenous and intraperitoneal injection of ([ 35S] sulphoamino)-heparin resulted in the appearance in the urine of unchanged ester together with substantial amounts of inorganic 35SO 4 2− ions. In contrast only minimal quantities of inorganic 35SO 4 2t ions were present in the urine following the injection of 2-deoxy-2-[ 35S] sul-phoamino- d-glucose which was rapidly excreted. No degradation of the sulphamate groupings of ([ 35S] sulphoamino)-chitosan and [ 35S] sulphaomino- l-serine occured when examined in the same way. The metabolism of ([ 35S] sulphoamino)-heparin was also investigated in rats with bile and ureter cannulae and analysis of urine, bile and blood samples revealed the ability of theses animals to degrade this compound with the appearance of inorganic 35SO 4 2− ions.

The metabolism of potassium dodecyl [35-S]sulphate in the rat.

The metabolic fate of potassium dodecyl [(35)S]sulphate was studied in rats. Intraperitoneal and oral administration of the ester into free-ranging animals were followed by the excretion of the bulk of the radioactivity in the urine within 12hr., approximately 17% being eliminated as inorganic [(35)S]sulphate. Similar results were obtained in experiments in which potassium dodecyl [(35)S]sulphate was injected intravenously into anaesthetized rats with bile-duct and ureter cannulae. Analysis of urinary radioactivity revealed the presence of a new ester sulphate (metabolite A). This metabolite was isolated, purified and subsequently identified as the sulphate ester of 4-hydroxybutyric acid by paper, thin-layer and gas chromatography, by paper electrophoresis and by comparison of its properties with those of authentic butyric acid 4-sulphate. The identity of the metabolite was confirmed by isotope-dilution experiments. When either purified metabolite A or authentic potassium butyric acid 4[(35)S]-sulphate was administered to free-ranging rats the bulk of the radioactivity was eliminated unchanged in the urine within 12hr., approx. 20% of the dose appearing as inorganic [(35)S]sulphate. Whole-body radioautography and isolated-liver-perfusion experiments implicated the liver as the major site of metabolism of potassium dodecyl [(35)S]sulphate. It is suggested that butyric acid 4-sulphate probably arises by omega-oxidation of dodecyl sulphate to a fatty acid-like compound, which is then degraded by beta-oxidation.