ArticleJournal of translational medicine2015
Febuxostat pretreatment attenuates myocardial ischemia/reperfusion injury via mitochondrial apoptosis.
Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Prevention of kidney function decline using uric acid-lowering therapy in chronic kidney disease patients: a systematic review and network meta-analysis.Clinical rheumatology · 2022Pooled it
- Febuxostat therapy in outpatients with suspected COVID-19: A clinical trial.International journal of clinical practice · 2020Trial
- Formulation, characterization and evaluation of cytotoxic potential for febuxostat loaded chitosomes against cervical cancer cells (Hela cells).Scientific reports · 2026Article
- Machine learning-based prediction of drug response in ischemia reperfusion animal model.Scientific reports · 2025Article
- Mechanism of xanthine oxidase in flap ischemia-reperfusion injury and advances in targeted therapy: a mini review.Frontiers in physiology · 2025Review
- Potential therapeutic targets in the prevention of testicular ischemia-reperfusion injury.Frontiers in reproductive health · 2025Review
- Article
- Febuxostat attenuates secondary brain injury caused by cerebral hemorrhage through inhibiting inflammatory pathways.Iranian journal of basic medical sciences · 2024Article
- Tissue accumulation of neutrophil extracellular traps mediates muscle hyperalgesia in a mouse model.Scientific reports · 2022Article
- High-Throughput mRNA Sequencing Reveals Potential Therapeutic Targets of Febuxostat in Secondary Injury After Intracerebral Hemorrhage.Frontiers in pharmacology · 2022Article
- Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase.Biomedicines · 2021Review
- Gout Pharmacotherapy in Cardiovascular Diseases: A Review of Utility and Outcomes.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2021Review
- The role of reactive oxygen species in cognitive impairment associated with sleep apnea.Experimental and therapeutic medicine · 2020Article
- Mitochondrial quality control mechanisms as molecular targets in cardiac ischemiaActa pharmaceutica Sinica. B · 2020Review
- Metabolomics analysis elucidates unique influences on purine / pyrimidine metabolism by xanthine oxidoreductase inhibitors in a rat model of renal ischemia-reperfusion injury.Molecular medicine (Cambridge, Mass.) · 2019Article
- Effects of febuxostat on atrial remodeling in a rabbit model of atrial fibrillation induced by rapid atrial pacing.Journal of geriatric cardiology : JGC · 2019Article
- Febuxostat inhibits TGF‑β1‑induced epithelial‑mesenchymal transition via downregulation of USAG‑1 expression in Madin‑Darby canine kidney cells in vitro.Molecular medicine reports · 2019Article
- COX6B1 relieves hypoxia/reoxygenation injury of neonatal rat cardiomyocytes by regulating mitochondrial function.Biotechnology letters · 2019Article
- Pretreatment with Total Flavonoid Extract from Dracocephalum Moldavica L. Attenuates Ischemia Reperfusion-induced Apoptosis.Scientific reports · 2018Article
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFebuxostat is a selective inhibitor of xanthine oxidase (XO). XO is a critical source of reactive oxygen species (ROS) during myocardial ischemia/reperfusion (I/R) injury. Inhibition of XO is therapeutically effective in I/R injury. Evidence suggests that febuxostat exerts antioxidant effects by directly scavenging ROS. The present study was performed to investigate the effects of febuxostat on myocardial I/R injury and its underlying mechanisms.
methodsWe utilized an in vivo mouse model of myocardial I/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of hypoxia/reoxygenation (H/R) injury. Mice were randomized into five groups: Sham, I/R (I/R + Vehicle), I/R + FEB (I/R + febuxostat), AL + I/R (I/R + allopurinol) and FEB (febuxostat), respectively. The I/R + FEB mice were pretreated with febuxostat (5 mg/kg; i.p.) 24 and 1 h prior to I/R. NRCs received febuxostat (1 and 10 µM) at 24 and 1 h before exposure to hypoxia for 3 h followed by reoxygenation for 3 h. Cardiac function, myocardial infarct size, serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), and myocardial apoptotic index (AI) were measured in order to ascertain the effects of febuxostat on myocardial I/R injury. Hypoxia/reperfusion (H/R) injury in NRCs was examined using MTT, LDH leakage assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The underlying mechanisms were determined by measuring ROS production, mitochondrial membrane potential (ΔΨm), and expression of cytochrome c, cleaved caspases as well as Bcl-2 protein levels.
resultsMyocardial I/R led to an elevation in the myocardial infarct size, serum levels of CK and LDH, cell death and AI. Furthermore, I/R reduced cardiac function. These changes were significantly attenuated by pretreatment with febuxostat and allopurinol, especially by febuxostat. Febuxostat also protected the mitochondrial structure following myocardial I/R, inhibited H/R-induced ROS generation, stabilized the ΔΨm, alleviated cytosolic translocation of mitochondrial cytochrome C, inhibited activation of caspase-3 and -9, upregulated antiapoptotic proteins and downregulated proapoptotic proteins.
conclusionsThis study revealed that febuxostat pretreatment mediates the cardioprotective effects against I/R and H/R injury by inhibiting mitochondrial-dependent apoptosis.
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