Isoniazid Protects Against Angiotensin II‐Induced Cardiac Hypertrophy in Sprague Dawley Rats
Bibliographic record
Abstract
Cytochrome P450 (CYP)-derived Arachidonic acid (AA) metabolites are reported to exhibit potent biological activities. Isoniazid (INH) is a well-known CYP modulator that can lead to alterations in cardiac CYP-mediated AA metabolism. We aimed to determine the effect of INH on cardiac CYP-mediated AA metabolism, and the biological effect of INH treatment on Angiotensin II (Ang II)-induced cardiac hypertrophy. Male Sprague Dawley rats were treated with INH (200 mg/kg/day), Ang II (450 ng/kg/min), or both for 2 weeks. Ang II-induced cardiac hypertrophy was assessed by heart weight to tibia length ratio and echocardiography. CYP expression was determined by real-time PCR and Western blot. CYP-derived AA metabolites were measured by liquid chromatography–electrospray ionization-mass spectrometry. Echocardiographic analysis showed that INH improved heart functions in addition to reversing the increase in heart weight to tibia length ratio caused by Ang II. The cardioprotective effect of INH was associated with an increased level of cardiac 19-HETE. In addition, INH significantly reduced the cardiotoxic AA metabolite, 20-HETE-induced by Ang II treatment. However, it caused a significant decrease in the cardioprotective AA metabolite, 14,15-EET. This demonstrates that INH alters the expression of cardiac CYP and their associated AA metabolites and partially protects against Ang II-induced cardiac hypertrophy. Our study further confirms the role of CYP, and their associated AA metabolites in cardiac hypertrophy development. This work was supported by Canadian Institutes of Health Research (CIHR) Grant to A.O.S; S.E is the recipient of the Libyan government scholarship.
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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 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".