“…This zonation creates nontrivial gradient profiles in the canalicular network that complicate deciphering the flux mechanism. A systematic study is under preparation. - Estradiol‐17‐glucuronide (E17G)‐induced cholestasis: We discussed E17G‐induced transient cholestasis in a Reply [ 2 ] ; the authors mention observations of bile acid concentrations in extrahepatic bile that neither prove nor disprove the existence of canalicular water flow. Rather, E17G was later shown to inhibit the bile acid transporter BSEP on hepatocytes and several ion pumps required for water efflux on cholangiocytes.
- Mannitol clearance: Deducing a “canalicular flow” from mannitol clearance assumes its (i) exclusively canalicular permeability and (ii) inertness with respect to bile flow.
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