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Updated: Jul 16, 2026
04:43
Targeted Knockdown of Genes in the Choroid Plexus
Published on: June 16, 2023
Phloracetophenone-induced choleresis in rats is mediated through Mrp2
Lukmanee Tradtrantip1, Pawinee Piyachaturawat, Carol J Soroka
1Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Summary
Phloracetophenone (THA) enhances bile flow independently of bile acids, suggesting osmotic effects. Its choleretic activity relies on multidrug resistance protein-2 (Mrp2) for excretion and reversal of cholestasis.
Area of Science:
- Hepatology
- Pharmacology
- Molecular Biology
Background:
- Phloracetophenone (2,4,6-trihydroxyacetophenone, THA) is a known choleretic agent.
- The precise mechanism by which THA enhances bile secretion remains largely unknown.
Purpose of the Study:
- To elucidate the mechanism of THA-induced bile secretion.
- To investigate the role of canalicular transporters, specifically multidrug resistance protein-2 (Mrp2), in THA's choleretic effect.
Main Methods:
- Isolated perfused rat liver model with stepwise THA infusions.
- Assessment of bile flow (BF) and excretion of bile acids, sulfobromophthalein (BSP), and disulfobromophthalein (DBSP).
- Studies in TR(-) rats lacking Mrp2 function and evaluation of THA's effect on estradiol-17beta-D-glucuronide-induced cholestasis.
Main Results:
- THA caused a dose-dependent, saturable increase in bile flow, independent of bile acid excretion.
- THA inhibited the biliary excretion of Mrp2 substrates (BSP and DBSP), suggesting competition for transport.
- THA's choleretic effect was abolished in Mrp2-deficient TR(-) rats, confirming Mrp2 dependence.
- THA partially reversed cholestasis induced by estradiol-17beta-D-glucuronide.
Conclusions:
- The choleretic activity of THA is critically dependent on the canalicular transporter Mrp2.
- THA likely stimulates bile flow through osmotic effects and may mitigate drug-induced cholestasis via Mrp2-mediated pathways.
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