D-Glucaro-1,4-lactone: Its excretion in the bile and urine and effect on the biliary secretion of β-glucuronidase after oral administration in rats
✍ Scribed by Andrew Macfadyen; Kang-Jey Ho
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 536 KB
- Volume
- 9
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
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 8-glucuronidase, which is believed to play a key role in the development of pigment gallstones. D-G~ucaro-1,4-lactone, 50 to 2,600 pmoles, 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 &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 B-glucuronidase activity. The maximal velocity of @-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 ~-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 8-glucuronidase activity. Oral administration of D-glucaro-1,4-1actone decreased biliary 8-glucuronidase concentration, slowed bile flow rate and hence decreased biliary B-glucuronidase secretion. The effect reached a maximum of 80% suppression at an oral dose of 1,000 pmoles or more of D-glucaro-1,4-1actone. The combined effect of the presence of ~-glucaro-1,4-lactone in the bile and the suppression of 8-glucuronidase secretion was the reduction of the endogenous 8-glucuronidase to 5% of its original activity. We therefore concluded that oral administration of D-glucaro-1,4-1actone markedly lowers biliary endogenous 8-glucuronidase activity due to both the presence of D-glucaro-1,4-lactone in the bile and the decrease in hepatic 8-glucuronidase secretion.