Abstract 19744: Protective Effect of Nrf2 on Ischemia-reperfusion Injury in Murine Heart Transplantation
Bibliographic record
Abstract
Background: Oxidative stress plays a critical role in mediating tissue injury and cellular apoptosis during ischemia-reperfusion injury (IRI). Nrf2 is a transcription factor regulating antioxidant defenses by inducing phase II enzymes, including superoxide dismutase (SOD). However, there are few studies investigating its role in heart transplantation (HTx). In this study, we examined the protective potential of Nrf2 and the Nrf2 inducer, Sulforaphane (SFN), against IRI using a murine neck HTx model. Methods: (1) in vitro study: We treated human coronary artery smooth muscle cells (HCASMC) with 25uM SFN for 24 hours and evaluated Nrf2 expression as well as whole cell SOD activity. (2) in vivo study: We gave 25mg/kg SFN on C57BL/6J wild-type (WT) and Nrf2 knockout (KO) mice, and measured Nrf2 expression and mitochondrial SOD activity on their hearts. (3) HTx study: WT mice were used as recipients, and WT and KO mice were used as donors. 25mg/kg SFN or saline were injected 1 day prior to surgery and after surgery. Donor hearts were perfused with 25uM SFN or saline and stored in the solution for 2 hours to induce IRI. Echocardiography was done after 24 hours reperfusion. Results: (1) SFN induced Nrf2 on HCASMC (1181.5±68.1 % control, p<0.01, n=4). SFN also increased whole cell SOD activity (112.5±2.93 vs 29.9±1.25 U/mg protein in control, p<0.01, n=4) (2) SFN induced Nrf2 in WT after 2 hours of injection (161.1±5.8 % control, p<0.01, n=4). SFN also increased mitochondrial SOD activity in WT after 24 hours of injection. However, this upregulation was absent in KO (Figure1). (3) The %FAC of donor hearts was significantly higher in WT-SFN than WT-Saline after 24 hours reperfusion. KO-Saline and KO-SFN showed similarly lower %FAC than WT (Figure2). Conclusion: Our results suggested that Nrf2 protects against ischemia-reperfusion injury in heart transplantation. The Nrf2 inducer Sulforaphane may represent novel therapy to prevent ischemia-reperfusion injury in heart transplantation. ![][1] [1]: /embed/graphic-1.gif
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".