The Effect of Serum Lipoproteins on Amiodarone Metabolism in Cultured Primary Rat Hepatocytes
Bibliographic record
Abstract
Abstract Purpose: To examine the effect of serum lipoproteins on amiodarone (AM) metabolism in cultured primary rat hepatocytes. Method: Primary rat hepatocytes were isolated from normal lipidemic (NL) or hyperlipidemic (HL) Sprague Dawley rats. All experimental groups were treated with AM (500 ng/mL) for 0–72h (n=18 wells for each time point). In preincubation groups, hepatocytes were pre-incubated for 24 h at 37°C with media or 5% NL or HL serum in media. After 24 h, the medium containing serum was removed and treatment was initiated with drug incubated with media alone. For serum co-incubation groups, the AM serum mixture was added to hepatocytes. Experiments were terminated at various time points by addition of 0.5 mL 1N NaOH to each well and samples collected in Eppendorf tubes and stored at −30°C until analyzed for the concentration of AM remaining. Results: In absence of serum, there was no significant difference in the area under the % AM recovering time curve (ARE) between the NL and HL hepatocytes over the time period from 0–72h. However, ARE from 0–24h in HL rat hepatocytes (1630±39.3 % h) was significantly higher than that of the NL rat hepatocytes (1409±57.2 % h). The co-incubation of NL serum led to a significant increase in the ARE in the NL hepatocytes compared to the incubations in the absence of the serum. The addition of HL sera, whether it be as pre- or co-incubations, led to significant increases in the ARE compared to media only and NL serum incubations. In addition the co-incubated NL hepatocytes had significantly higher (6288% h) ARE when exposed to HL serum than the pre-incubated (4552 % h) cells. Conclusion: Serum pre-incubation decreased the amiodarone metabolism in cultured primary hepatocytes due to down regulation of CYP enzymes. Serum co-incubation resulted in significantly lower AM metabolism than the corresponding pre-incubation groups due to a decrease in AM unbound fraction. The hypothesized enhanced association of drug with VLDL and LDL fractions in co-incubation with HL serum compared to NL serum was not sufficient to increase the uptake of the drug into hepatocytes and increase the drug metabolism significantly between those two groups.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".