Interaction of the HMG-CoA Reductase Inhibitor Lovastatin and Nitric Oxide in Cardiomyocyte Cell Death
Bibliographic record
Abstract
AIM: The objective of this study was to examine the interaction ofa 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) with a nitric oxide (NO) donor from the perspective of the impact on cardiomyocyte cell viability. METHODS: Embryonic chick cardiomyocytes in culture were treated with a wide range of concentrations of sodium nitroprusside (SNP), which releases NO and also generates toxic reactive nitrogen species. SNP was combined with the HMG-CoA reductase inhibitor lovastatin and cell viability was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. RESULTS: SNP and lovastatin each produced a significant (p < 0.01) concentration-dependent increase in cell death. Using SNP concentrations at or below the ED50, SNP (0.01, 0.1 or 0.5 mmol/l) increased the amount of cell death when combined with lovastatin (1, 10, 50 and 100 micromol/l). At lovastatin concentrations of 50 micromol/l and less, the amount of cell death was consistently similar to the arithmetic sum of SNP and lovastatin, suggesting that there was an additive and not synergistic relationship between SNP and lovastatin. In combination with lovastatin (100 micromol/l), however, the amount of cell death was consistently lower than the calculated expected value and suggested saturation of a common mechanism. The combination of SNP and lovastatin produced the characteristic microscopic changes of apoptosis. Considering that both SNP and lovastatin can activate caspase-3, cells were treated with the caspase-3 inhibitor Ac-DEVD-CHO. This inhibitor produced a significant (p < 0.05) and consistent 30% reduction in the amount of cell death induced by SNP and lovastatin. CONCLUSION: These data suggest that the cardiomyocyte toxicity from NO continues to be evident uninterrupted by and not accentuated by the presence of an HMG-CoA inhibitor. The cardiac adverse effect of each of these agents utilizes a common pathway involving caspase-3 so that their cardiotoxicity can be blunted by a caspase-3 inhibitor.
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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 | 0.000 | 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 | 0.000 | 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".