Involvement of Oxidative Stress and Antioxidants in Modification of Cardiac Dysfunction Due to Ischemia–Reperfusion Injury
Bibliographic record
Abstract
Delayed reperfusion of the ischemic heart (I/R) is known to impair recovery of cardiac function and produce a wide variety of myocardial defects including ultrastructural damage, metabolic alterations, subcellular Ca2+-handling abnormalities, activation of proteases and changes in cardiac gene expression. Although I/R-injury has been reported to induce the formation of reactive oxygen species (ROS), inflammation and intracellular Ca2+-overload, generation of oxidative stress is considered to play a critical role in the development of cardiac dysfunction. There occurs an increase in the production of superoxide and hydroxyl radicals as well as oxidants such as hydrogen peroxide and hypochlorous acid in hearts subjected to I/R-injury. In fact, mitochondria are a major source of excessive production of ROS in I/R hearts due to impairment in the electron transport system as well as activation of xanthine oxidase, monoamine oxidase and NADPH oxidase. Nitric oxide synthase, mainly present in the endothelium, is also activated due to I/R injury to produce nitric oxide, which upon combination with superoxide radicals, generates nitrosative stress. Alterations in cardiac function, sarcolemma and sarcoplasmic reticulum Ca2+-handling activities, and mitochondrial oxidative phosphorylation as well as protease activation due to I/R-injury are simulated upon exposing the heart to oxyradical generating system (xanthine plus xanthine oxidase) or H2O2. On the other hand, the activation of endogenous antioxidants such as superoxide dismutase, catalase and glutathione peroxidase as well as the concentration of a transcription factor (Nrf2), which modulates the expression of various endogenous antioxidants, are depressed due to I/R injury in hearts. Furthermore, pretreatment of hearts with antioxidants such as catalase plus superoxide dismutase, N-acetylcysteine and mercaptopropionylglycerine was observed to attenuate the I/R-induced subcellular Ca2+-handling and changes in Ca2+-regulatory activities as well as depress protease activation and improve the recovery of cardiac function. These observations indicate that oxidative stress is intimately involved in the pathological effects of I/R-injury and different antioxidants attenuate I/R-induced subcellular alterations and improve the recovery of cardiac function. Thus, there is a challenge to develop safe and effective antioxidants as well as agents for upregulating the expression of endogenous antioxidants for the therapy of I/R-injury.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".