Abstract
Sulfated glycolithocholic acid (SGLC) causes intrahepatic cholestasis in experimental animals. In 2 patients with intermittent cholestasis during symptom-free periods a marked postprandial rise in serum SGLC was observed, which could be prevented by adding cholestyramine to the testmeal. This suggests an intestinal origin of SGLC. We therefore studied the absorption characteristics of (S)LC conjugates in vivo. Rats were provided with permanent catheters in the bile duct and the duodenum. Intraduodenal infusions of 14C-labeled gly and tau conjugated LC and their 3α-sulfated esters were performed after 4 days of bile drainage. Excretion of 14C-labeled bile acids in bile, urine and faeces was measured over 24h. At a dose of 125 nmol/min GLC, TLC, SGLC and STLC were efficiently absorbed. In contrast to their unsulfated precursors, SGLC and STLC were not metabolized in the liver. Replacement of NaCl in the infusate by CaCl2 reduced the absorption of SGLC and STLC with 63% and 52% resp., that of GLC and TLC with 19% and 22%. Absorption of taurocholic acid (TC) was not affected by CaCl2.
Absorption of SGLC was dose-dependent, and not affected by co-infusion of rat bile or an equimolar TC solution.
SGLC and STLC may undergo enterohepatic circulation, thereby continuously exposing the liver to their hepatotoxic actions. In presence of calcium, however, their absorption is impaired.
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Vonk, R., Kuipers, F., Havinga, R. et al. INTESTINAL ABSORPTION OF SULFATED LITHOCHOLIC ACID CONJUGATES: EFFECT OF CALCIUM. Pediatr Res 19, 1074 (1985). https://doi.org/10.1203/00006450-198510000-00037
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DOI: https://doi.org/10.1203/00006450-198510000-00037