Nrf2‐disrupted mice exhibits heightened liver injury induced by lithocholic acid
Bibliographic record
Abstract
Bile acid toxicity contributes to the pathogenesis of cholestasis. Lithocholic acid (LCA), the most toxic bile acid, induces cholestatic liver injury in rodents. On cultured hepatocytes we showed that LCA could activate the oxidative stress‐responsive Nrf2, triggering adaptive responses to mitigate resultant cell injury. Using Nrf2 disrupted (Nrf2‐/‐) mice, the in vivo role of Nrf2 in LCA‐induced hepatotoxicity was determined. Mice were injected (i.p.) with 125 mg/kg LCA. At 8 hours and 4 days of LCA treatment, hepatic expression of Nrf2‐target, cytoprotective genes including thioredoxin reductase 1, glutamate cysteine ligase subunits, glutathione S‐transferases, NAD(P)H: quinone oxidoreductase 1 and multidrug resistance‐associated proteins 3 and 4 was significantly enhanced in the wildtype, as compared to the Nrf2‐/‐ mice. Sex dimorphic influence in induction of Nrf2‐target genes was noticed. The blunted response in cytoprotective gene induction in Nrf2‐/‐ mice was accompanied by a more severe liver injury as evidenced by presence of multifocal liver necrosis, inflamed bile ducts, and significant elevated liver injury markers alanine aminotransferase and alkaline phosphatase. In conclusion, Nrf2 plays a crucial protective role against LCA‐induced liver injury by regulating cytoprotective genes which promotes cell survival upon toxic bile acid insults. Funded by CIHR
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".