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Bile salts as endogenous digitalis like factors
Summary
Bile salts contribute significantly to digitalis-like factors in bile but not plasma. These endogenous compounds influence assays for digoxin and affect Na,K-ATPase activity, distinct from typical digitalis interactions.
Area of Science:
- Biochemistry
- Pharmacology
- Physiology
Background:
- Digitalis-like factors (DLFs) are endogenous compounds that can interfere with digoxin assays and influence cardiovascular function.
- The origin and specific nature of DLFs, particularly in bile and plasma, remain incompletely understood.
Purpose of the Study:
- To investigate the contribution of bile salts to DLFs in human bile and plasma.
- To characterize the interaction of bile salts with digoxin antibodies and Na,K-ATPase.
Main Methods:
- Radioimmunoassay of digoxin in bile and plasma samples.
- Assay of Na,K-ATPase inhibition and [3H]-ouabain displacement.
- High-performance liquid chromatography (HPLC) for DLF fractionation.
Main Results:
- Bile samples contained significant DLF activity (23-85 nmol digoxin equivalents/L), with bile salts accounting for 50-79% of this activity.
- HPLC analysis revealed DLF peaks in bile co-eluting with various bile salt standards, representing 78% of DLF activity in bile.
- In plasma from patients with hepatic and renal failure, bile salts accounted for only 2-7% of DLF activity.
Conclusions:
- Bile salts are identified as endogenous compounds contributing substantially to DLF activity in human bile.
- These bile salts interact with digoxin antibodies and Na,K-ATPase but do not act via simple competitive ligand binding.
- Bile salts are a significant source of DLF activity in bile, but their contribution to plasma DLF activity is minimal.