Antioxidant N‐acetylcysteine restores myocardial Mn‐SOD activity and attenuates left ventricular diastolic dysfunction in diabetic rats
Bibliographic record
Abstract
Manganese‐containing superoxide dismutase (Mn‐SOD) plays a critical role in guarding against mitochondrial oxidative stress (OS). Abnormal myocardial mitochondrial metabolism of reactive oxygen species plays an important role in the pathogenesis of diabetic cardiac dysfunction. We hypothesized that chronic treatment with N‐acetylcysteine (NAC), an antioxidant, would normalize hyperglycemia induced inactivation of Mn‐SOD and attenuate myocardial dysfunction. Control and streptozotozin‐induced diabetic rats were treated (CT, DT) or untreated (C, D) with NAC in drinking water for 8 weeks. Myocardial Mn‐SOD activity, but not Mn‐SOD protein expression, in D rats was significantly reduced while levels of OS as determined by myocardial free 15‐F2t‐isoprostane was increased as compared to all other groups. This was accompanied by increased membrane translocation of p67phox, a cytosolic subunit of the NAD(P)H oxidase whose activation may contribute to the elevated OS in diabetes. A decrease in left ventricular maximum relaxation (‐dP/dT) and an increase in the t1/2 to maximum relaxation were found in D rats. NAC normalized or attenuated the changes seen in D group. The results suggest that OS‐mediated inactivation of myocardial Mn‐SOD may contribute to the development of myocardial diastolic dysfunction in diabetes. This study was funded by GIA from Canadian Diabetes Association and a Program Grant from the Heart & Stroke Foundation of BC and Yukon, Canada. ZX and JJ are supported by CIHR/Rx &D HRF.
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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) | 0.001 | 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".