Cytochrome P450 2A5 expression in a G6PD‐deficient mouse model of oxidative stress
Bibliographic record
Abstract
Murine hepatic cytochrome P450 2A5 (CYP2A5), unlike most CYP enzymes, is upregulated during hepatitis and hepatotoxicity. To determine if oxidative stress is responsible for this induction, glucose‐6‐phosphate dehydrogenase (G6PD)‐deficient mice, that are more susceptible to oxidative stress, were treated with the prototypical CYP2A5 inducer pyrazole. Compared to normal mice, G6PD‐deficient mice had 3, 1.6, and 5 times greater induction of CYP2A5 mRNA, protein, and activity, respectively. Involvement of oxidative stress was determined using markers of oxidative damage and expression of oxidant‐responsive genes. Although no significant elevation in protein carbonyl groups or glutathione peroxidase and superoxide dismutase transcripts were observed, NADPH quinone oxidoreductase 1, which protects against oxidative stress and redox cycling, was increased by pyrazole. Glutathione‐S‐transferase (GST) alpha, mu, and pi mRNA levels were also elevated by pyrazole, with GST pi showing 1.9 times greater induction in G6PD‐deficient mice. Glucose‐regulated protein 78, an endoplasmic reticulum stress protein, showed a 1.7 fold greater response to pyrazole in deficient mice. These results suggest that conditions leading to upregulation of CYP2A5 are complex and factors other than oxidative stress may be involved in regulation of CYP2A5. Supported by the Natural Sciences and Engineering Research Council of Canada.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".