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Febuxostat pretreatment attenuates myocardial ischemia/reperfusion injury via mitochondrial apoptosis

Overview of attention for article published in Journal of Translational Medicine, July 2015
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  • Good Attention Score compared to outputs of the same age and source (65th percentile)

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1 patent

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Title
Febuxostat pretreatment attenuates myocardial ischemia/reperfusion injury via mitochondrial apoptosis
Published in
Journal of Translational Medicine, July 2015
DOI 10.1186/s12967-015-0578-x
Pubmed ID
Authors

Shulin Wang, Yunpeng Li, Xudong Song, Xianbao Wang, Cong Zhao, Aihua Chen, Pingzhen Yang

Abstract

Febuxostat 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. We 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. Myocardial 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. This study revealed that febuxostat pretreatment mediates the cardioprotective effects against I/R and H/R injury by inhibiting mitochondrial-dependent apoptosis.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 46 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 13%
Student > Master 5 11%
Student > Bachelor 5 11%
Researcher 4 9%
Other 4 9%
Other 9 20%
Unknown 13 28%
Readers by discipline Count As %
Medicine and Dentistry 13 28%
Pharmacology, Toxicology and Pharmaceutical Science 4 9%
Biochemistry, Genetics and Molecular Biology 4 9%
Agricultural and Biological Sciences 3 7%
Nursing and Health Professions 2 4%
Other 6 13%
Unknown 14 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 October 2021.
All research outputs
#6,957,322
of 22,816,807 outputs
Outputs from Journal of Translational Medicine
#1,086
of 3,992 outputs
Outputs of similar age
#81,098
of 263,464 outputs
Outputs of similar age from Journal of Translational Medicine
#33
of 103 outputs
Altmetric has tracked 22,816,807 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 3,992 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.5. This one has gotten more attention than average, scoring higher than 71% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 263,464 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
We're also able to compare this research output to 103 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.