D-glucaro-1,4-lactone: its excretion in the bile and urine and effect on the biliary secretion of beta-glucuronidase after oral administration in rats.
This experiment was designed to test the hypothesis that orally administered D-glucaro-1,4-lactone might be excreted in the bile and thus suppress the activity of biliary beta-glucuronidase, which is believed to play a key role in the development of pigment gallstones. D-Glucaro-1,4-lactone, 50 to 2,600 mu moles, was fed to adult Sprague-Dawley rats which had a bile fistula and were kept in metabolic cages for bile and urine collection. A total of 21 feeding experiments were carried out. Quantitation of D-glucaro-1,4-lactone and total D-glucaric acid as the sum of D-glucaric acid and its lactones in the bile and urine involved extraction of bile with tetrahexylammonium chloride, adjustment of pH, boiling and determination of percentage inhibition of beta-glucuronidase activity. The maximal velocity of beta-glucuronidase in the bile was also determined by the enzyme kinetic method. The results showed that 11% of administered D-glucaro-1,4-lactone was excreted in the urine and only 0.2% in the bile, with D-glucaro-1,4-lactone accounting for 20% of the total excreted D-glucaric acid. The concentration and excretory rate of total D-glucaric acid and D-glucaro-1,4-lactone in the urine, but not in the bile, were proportional to the amount of D-glucaro-1,4-lactone fed. The mean concentration of D-glucaro-1,4-lactone in the bile after feeding was 0.06 mM, which was capable of suppression of 75% of beta-glucuronidase activity. Oral administration of D-glucaro-1,4-lactone decreased biliary beta-glucuronidase concentration, slowed bile flow rate and hence decreased biliary beta-glucuronidase secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Macfadyen
A
A
Department of Pathology, University of Alabama, Birmingham Medical Center 35233.
Ho
K J
KJ
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000201:enzymology / Q000378:metabolism*; D005937:Glucaric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D005966:Glucuronidase / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013400:Sugar Acids / Q000378:metabolism*
D013400:Sugar Acids; C009194:saccharolactone; D005966:Glucuronidase; D005937:Glucaric Acid