Mitigation of nitrosative stress and inflammation by Vitamin C in cardiomyopathy
Bibliographic record
Abstract
Background Oxidative/nitrosative stress is being linked as a key event in development of various cardiovascular diseases. Increase in the generation of reactive oxygen and nitrogen species is considered as a major trigger for cellular and tissue injury in the heart leading to myocardial dysfunction in general and doxorubicin (Dox) ‐ induced heart failure in particular. Previously we have shown that Vitamin C (Vit C), a very potent antioxidant, reduced Dox‐induced oxidative stress in isolated cardiomyocytes. However the role of Vit C in mitigation of cardiac nitrosative stress and inflammation needs to be understood. The aim of present study is to understand role of Vit C on cardiac nitrosative stress and inflammation. Methods Cardiomyocytes isolated from adult Sprague‐Dawley rats were treated with predetermined doses of Vit C (25 μM), Dox (10 μM) or Vit C (25 μM) + Dox (10 μM) for in vitro studies. To understand the effect of Vit C in vivo, adult male Wistar rats were treated with Vit C (50 mg/kg bw orally daily) for 6 weeks or Dox (15mg/kg bw given intraperitoneally in six equal doses for three weeks) or combination treatment with Vit C + Dox. At the end of 6 weeks, animals were euthanized and hearts and blood were collected for further analysis. Results Dox treatment increased levels of peroxynitrite in isolated cardiomyocytes and this effect was significantly reduced by Vit C co‐treatment. Both invitro and invivo, Dox induced an increase in levels of Nitric oxide, Nitric oxide synthase (NOS) activity and protein nitrosylation. These in vitro and invivo effects were blocked by Vit C. Dox caused an increased protein expression of inducible NOS which was prevented by Vit C, whereas expression of endothelial NOS was reduced. Treatment with Dox showed increase in levels of inflammatory cytokine TNFα and a decrease in the anti‐inflammatory cytokine IL10. Vit C co‐treatment prevented deleterious effects of Dox by reduction in levels of TNFα and increased levels of IL10. Conclusion Based on these results, it is suggested that an attenuation of major triggers of Dox‐induced cardiotoxicity by Vit C would be beneficial in protecting the heart from cardiac side effect of chemotherapy. Support or Funding Information CIHR and GETS, University of Manitoba.
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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) | 0.000 | 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 | 0.001 | 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".