Effects of Long-Term Hepatic Ischemia-Reperfusion Injury on the Function of P-glycoprotein in vivo in Rats
Bibliographic record
Abstract
PURPOSE: Ischemia-reperfusion injury is a common complication in liver surgery with oxidative stress related graft failure as a potential complication. The oxidative stress could affect hepatic drug transporters such as P-glycoprotein, which is crucial in the hepatic clearance of certain immunosuppressant drugs. Thus,, it is important to study its function after ischemia-reperfusion injury in vivo. Rhodamine 123 is a fluorescent substrate of P-glycoprotein and its hepatic disposition can be visualized using multiphoton microscopy in vivo using anaesthetized animals. The aim of this study was to investigate the effect of long-term ischemia-reperfusion injury on P-glycoprotein function in hepatocytes using in vivo multiphoton microscopy. METHODS: Localized ischemia was induced for 1 hour in rats. The liver was reperfused for 4, 24, 48 hours or 1 week, where-after rhodamine 123 was injected intravenously. Multiphoton microscopy imaged the liver and bile was collected continuously up to 6 hours following drug administration. The liver was harvested for histology and protein expression of P-glycoprotein. RESULTS: Ischemia-reperfusion injury resulted in extensive liver damage, inflammatory cell infiltration and apoptosis in the midzonal and centrilobular regions of the liver acinus. P-glycoprotein protein expression decreased. Cellular concentration of rhodamine 123 increased as visualized by multiphoton microscopy, which was confirmed with decreased excretion of rhodamine 123 in collected bile. CONCLUSIONS: This study showed reduced function of P-glycoprotein in ischemia-reperfusion injury as reflected by decreased biliary excretion of Rhodamine 123, as well as reduced protein expression of the transporter. Multiphoton microscopy could be used to visualize and quantitate the intracellular levels of rhodamine 123. These findings stipulate the importance of using multiphoton microscopy to understand transmembrane drug flux and reflect on careful drug dosing after hepatic surgery.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".