Nitroprusside induces cardiomyocyte death: interaction with hydrogen peroxide
Bibliographic record
Abstract
We examined the hypothesis that sodium nitroprusside (SNP) produces cell death in cardiomyocytes through generation of H(2)O(2). Embryonic chick cardiomyocytes in culture were treated with SNP, and cell viability was assessed by trypan blue, MTT assay, and fluorescent activated cell sorting (FACS) analysis. SNP for 24 h induced a significant (P < 0.001) dose-dependent loss of cell viability. On MTT assay, the half-maximal effective concentration was 0.53 mM (confidence interval 0.45-0.59 mM). SNP-treated cardiomyocytes displayed characteristic microscopic features of apoptosis: reduced cell size, nuclear disintegration, and membrane bleb formation. FACS analysis demonstrated SNP-induced apoptosis as well as cell changes consistent with necrosis. The proportion of cells with nuclear changes of apoptosis, identified by propidium iodide (PI) staining of permeabilized cells, increased significantly (P < 0.05) after 0.5 mM SNP for 24 h. The proportion of apoptotic cells, characterized by dual staining of intact cardiomyocytes with fluorescein diacetate and PI, was significantly (P < 0.05) increased after treatment with 0.5 mM SNP for 24 h. SNP metabolism and NO production was suggested by the significant (P < 0.05) increase in nitrite generation in the media with 0.5 mM SNP compared with control. SNP-mediated H(2)O(2) production was implicated in the mechanism of SNP-induced cell death. First, SNP produced a significant (P < 0.05) increase in H(2)O(2) detected in the media after 6 or 24 h of SNP treatment. Second, catalase completely blocked the reduction of cell viability induced by 0.1 mM SNP and significantly (P < 0.05) blunted the effect of 0.5 mM SNP. In contrast, the iron chelator deferoxamine did not alter SNP-induced loss of cell viability. FACS analysis showed that the combination of low concentrations of H(2)O(2) (10(-8) M) that did not alter cell viability augmented SNP-induced apoptosis. In contrast, the amount of necrotic cell death was unchanged by the combination of H(2)O(2) and SNP. H(2)O(2) plus SNP produced a dramatic alteration in cell structure with greater membrane bleb formation, shrunken cells, and more intense cytosolic acridine orange staining and nuclear fragmentation than either agent alone. These data indicate the vulnerability of cardiomyocytes to SNP and suggest the involvement of H(2)O(2) in the pathogenesis of SNP-induced cardiomyocyte cell death. Establishing apoptosis as a component of the type of cell death induced by SNP permitted the recognition that SNP-induced apoptosis was increased by chronic treatment with low (subtoxic) concentrations of H(2)O(2).
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 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".