ArticleMedical science monitor : international medical journal of experimental and clinical research2016
Chemical Chaperone 4-Phenylbutyric Acid Reduces Cardiac Ischemia/Reperfusion Injury by Alleviating Endoplasmic Reticulum Stress and Oxidative Stress.
Article in Medical science monitor : international medical journal of experimental and clinical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Organelle network dysfunction in primary cardiomyopathy: An integrated perspective on pathogenesis and therapeutics.Journal of molecular and cellular cardiology plus · 2026Review
- Polarized Light Microscopy for Quantitative Assessment of Sarcomere-Scale Structural Order in Cardiac Tissue.Journal of biophotonics · 2026Article
- Homocysteine-induced endothelial dysfunction through mediating endoplasmic reticulum stress.The Journal of international medical research · 2026Article
- Linking Heat Stress to Impaired Cardiac Repair: The ER Stress-Angiogenesis Axis as a Critical Barrier.International journal of molecular sciences · 2026Review
- ER stress inhibitor 4PBA attenuates hindlimb unloading-induced cardiac mitochondrial and metabolic dysfunction.Pflugers Archiv : European journal of physiology · 2025Article
- Review
- Sestrin2 Attenuates Myocardial Endoplasmic Reticulum Stress and Cardiac Dysfunction During Ischemia/Reperfusion Injury.Journal of the American Heart Association · 2024Article
- Targeting selective autophagy and beyond: From underlying mechanisms to potential therapies.Journal of advanced research · 2024Review
- Lipotoxicity, ER Stress, and Cardiovascular Disease: Current Understanding and Future Directions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Endoplasmic reticulum stress and alterations of peroxiredoxins in aged hearts.Mechanisms of ageing and development · 2023Article
- Generation of resolving memory neutrophils through pharmacological training with 4-PBA or genetic deletion of TRAM.Cell death & disease · 2022Article
- Reversing mitochondrial defects in aged hearts: role of mitochondrial calpain activation.American journal of physiology. Cell physiology · 2022Article
- Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis.Biomedicines · 2022Review
- Recent Advances on Drug Development and Emerging Therapeutic Agents Through Targeting Cellular Homeostasis for Ageing and Cardiovascular Disease.Frontiers in aging · 2022Review
- Inhibition of the unfolded protein response reduces arrhythmia risk after myocardial infarction.The Journal of clinical investigation · 2021Article
- Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases.Nature reviews. Cardiology · 2021Review
- Preliminary results of PBA-loaded nanoparticles development and the effect on oxidative stress and neuroinflammation in rats submitted to a chemically induced chronic model of MSUD.Metabolic brain disease · 2021Article
- Article
- Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments.Oxidative medicine and cellular longevity · 2021Review
- Targeting ER stress and calpain activation to reverse age-dependent mitochondrial damage in the heart.Mechanisms of ageing and development · 2020Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND Cardiovascular diseases are the leading cause of death in many countries and myocardial ischemia-reperfusion (I/R) injury is the cause of many serious heart diseases. Recent reports suggested that endoplasmic reticulum (ER) stress is associated with the progress of ischemia/reperfusion (I/R) injury. In a previous study, we illustrated that 4-phenylbutyric acid (4-PBA) reduces I/R-induced cell death in vitro through inhibiting the ER stress-initiated cell apoptosis. In the present study we investigated whether 4-PBA improves heart function in isolated rat hearts subjected to I/R and elucidated the potential mechanisms involved in 4-PBA-induced cardioprotective effects. MATERIAL AND METHODS The isolated rat hearts were subjected to global ischemia and reperfusion in the absence or presence of 4-PBA. Hemodynamic parameters (LVSP, LVEDP, ±dP/dtmax, and HR) were monitored and histopathological examination was applied. The biomarkers related to oxidative stress were detected by LDH, ROS, MDA, CK, SOD, and GSH-Px kits. A TUNEL apoptosis assay kit was used to detect apoptosis. The expression levels of ER stress and apoptosis proteins were evaluated by Western blotting. RESULTS We found that 4-PBA (5 mM, 10 mM) pretreatment significantly attenuated cardiac dysfunction and depressed oxidative stress induced by I/R. Moreover, I/R activated the ER stress proteins Grp78 and PERK, which are all decreased by 4-PBA. 4-PBA pretreatment also inhibited the expression of CHOP, Caspase-12, and Bax, reduced the phosphorylation of JNK, and enhanced the expression of anti-apoptotic protein Bcl-2. CONCLUSIONS We elucidated the significant protective effects of 4-PBA against I/R injuries by inhibition of ER stress, oxidative stress, and their associated apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.