Related Experiment Video

Updated: Apr 12, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

9.7K

Hepatocellular Shuttling and Recirculation of Sorafenib-Glucuronide Is Dependent on Abcc2, Abcc3, and Oatp1a/1b

Aksana Vasilyeva1, Selvi Durmus2, Lie Li1

  • 1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.

Cancer Research
|May 9, 2015
PubMed

Insights

Hepatocyte hopping, a liver detoxification process, allows cancer drug sorafenib glucuronide to shuttle between liver cells and circulation. This process, involving transporters and gut bacteria, impacts drug persistence and detoxification.

Area of Science:

  • Pharmacology
  • Hepatology
  • Drug Metabolism

Background:

  • The "hepatocyte hopping" process describes liver detoxification via shuttling of endogenous compounds like bilirubin glucuronide.
  • This involves transporter-mediated efflux from hepatocytes and subsequent re-uptake into liver cells.

Purpose of the Study:

  • To investigate if xenobiotic glucuronides, specifically of the anticancer drug sorafenib, also undergo hepatocyte hopping.
  • To elucidate the role of transporters and gut microbiota in the disposition of sorafenib glucuronide.

Main Methods:

  • Utilized transporter-deficient mouse models to study sorafenib-glucuronide transport.
  • Analyzed the efflux and re-uptake mechanisms of sorafenib-glucuronide in hepatocytes.
  • Investigated the role of microbial enzymes in the gut lumen on sorafenib-glucuronide.

Main Results:

  • Sorafenib-glucuronide is extruded from hepatocytes via Abcc2 (to bile) or Abcc3 (to circulation).
  • Oatp1a/1b transporters facilitate efficient re-uptake of sorafenib-glucuronide into neighboring hepatocytes.
  • Gut microbial enzymes cleave excreted sorafenib-glucuronide to sorafenib, which is reabsorbed, prolonging systemic exposure.

Conclusions:

  • The hepatocyte hopping mechanism is relevant for the detoxification of anticancer drugs like sorafenib that undergo hepatic glucuronidation.
  • This shuttling process, involving transporters and gut microbiota, contributes to the persistence of sorafenib in systemic circulation.
  • Hepatocyte hopping represents a novel concept in clinical pharmacology with implications for targeted cancer drug therapy.

More Related Videos

In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion12:35

In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion

Published on: November 10, 2011

19.8K
Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats08:55

Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats

Published on: April 15, 2016

10.0K

Related Concept Videos

Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
372
Hepatic Drug Excretion: Enterohepatic Cycling01:17

Hepatic Drug Excretion: Enterohepatic Cycling

Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
3.4K
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
150
Drug Elimination by Renal Route: Tubular Secretion01:15

Drug Elimination by Renal Route: Tubular Secretion

Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
3.8K
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
1.6K
Drug Elimination: Non-Renal Routes01:23

Drug Elimination: Non-Renal Routes

The liver plays a pivotal role in eliminating drugs and their metabolites, primarily through a process known as biliary excretion. This process involves the hepatocytes, the primary cells in the liver that generate bile. A range of transporters actively expels polar drugs or hydrophilic drug metabolites into the bile, which transports the drugs and metabolites into the small intestine. From here, they are eventually expelled from the body through feces. In some instances, the original drug or a...
3.6K