Use of Sandwich-Cultured Hepatocytes To Evaluate Impaired Bile Acid Transport as a Mechanism of Drug-Induced Hepatotoxicity
Bibliographic record
Abstract
Drug-induced liver toxicity is a significant problem in drug development and clinical practice, yet its mechanisms are not well understood. Growing evidence suggests that inhibition of bile acid transport may be one mechanism of hepatotoxicity. A number of hepatic transporters work in concert to transport bile acids and xenobiotics from blood to bile, and many drugs have been shown to perturb this process with detrimental consequences. Hepatocytes cultured in a sandwich configuration maintain transporter activity and liver-specific metabolic functions; thus, the sandwich-cultured hepatocyte model represents a useful tool for evaluating hepatotoxicity caused by interference with hepatic transporters. As an example, the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist troglitazone is one such drug that has been shown to inhibit bile acid transport in vitro. Data presented in this manuscript indicate that troglitazone inhibits both basolateral uptake and canalicular excretion of taurocholate in a concentration-dependent manner in both sandwich-cultured and suspended human and rat hepatocytes. These data confirm both the interaction of troglitazone with bile acid transporters in hepatocytes and the utility of the sandwich-cultured hepatocyte model to study such interactions.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".