ArticleTransplantation2012
In vivo hypoxic preconditioning protects from warm liver ischemia-reperfusion injury through the adenosine A2B receptor.
Article in Transplantation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Hypoxia preconditioning attenuates lung injury after thoracoscopic lobectomy in patients with lung cancer: a prospective randomized controlled trial.BMC anesthesiology · 2019Trial
- Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation.EBioMedicine · 2018Trial
- PlanHab Study: Consequences of combined normobaric hypoxia and bed rest on adenosine kinetics.Scientific reports · 2018Trial
- Purinergic signaling and cholangiocyte regeneration: a new frontier in ischemic liver injury.Frontiers in transplantation · 2025Review
- Adenosine receptor A2b confers ovarian cancer survival and PARP inhibitor resistance through IL-6-STAT3 signalling.Journal of cellular and molecular medicine · 2023Article
- Antihypoxic oxygenation agents with respiratory hyperoxia to improve cancer immunotherapy.The Journal of clinical investigation · 2020Review
- Adenosine A2a Receptor Stimulation Attenuates Ischemia-Reperfusion Injury and Improves Survival in A Porcine Model of DCD Liver Transplantation.International journal of molecular sciences · 2020Article
- Pre-conditions for eliminating mitochondrial dysfunction and maintaining liver function after hepatic ischaemia reperfusion.Journal of cellular and molecular medicine · 2017Review
- An Evaluation of Ischaemic Preconditioning as a Method of Reducing Ischaemia Reperfusion Injury in Liver Surgery and Transplantation.Journal of clinical medicine · 2017Review
- Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration.The Journal of biological chemistry · 2016Article
- Immunologic Consequences of Hypoxia during Critical Illness.Anesthesiology · 2016Article
- Hypoxia-inducible factors as molecular targets for liver diseases.Journal of molecular medicine (Berlin, Germany) · 2016Review
- Hypoxemic reperfusion of ischemic states: an alternative approach for the attenuation of oxidative stress mediated reperfusion injury.Journal of biomedical science · 2016Review
- I drink for my liver, Doc: emerging evidence that coffee prevents cirrhosis.F1000Research · 2015Review
- Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases.Nature reviews. Drug discovery · 2014Review
- The Role of Ectonucleotidases CD39 and CD73 and Adenosine Signaling in Solid Organ Transplantation.Frontiers in immunology · 2014Review
- Hypoxic preconditioning stimulates angiogenesis in ischemic penumbra after acute cerebral infarction.Neural regeneration research · 2013Article
- Equilibrative nucleoside transporter (ENT)-1-dependent elevation of extracellular adenosine protects the liver during ischemia and reperfusion.Hepatology (Baltimore, Md.) · 2013Article
- Biological implications of extracellular adenosine in hepatic ischemia and reperfusion injury.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2013Review
- Signaling through hepatocellular A2B adenosine receptors dampens ischemia and reperfusion injury of the liver.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundLiver ischemia-reperfusion injury (IRI) is a known risk factor for the postoperative outcome of patients undergoing liver surgery/transplantation. Attempts to protect from organ damage require multidisciplinary strategies and are of emerging interest in view of patients with higher age and American Society of Anesthesiology status. Ischemic preconditioning has been successfully applied to prevent from IRI during liver resection/transplantation. Because even short periods of ischemia during preconditioning inevitably lead to hypoxia and formation of anti-inflammatory/cytoprotective acting adenosine, we reasoned that short nonischemic hypoxia also protects against hepatic IRI.
methodsMice underwent hypoxic preconditioning (HPC) by breathing 10% oxygen for 10 min followed by 10 min of 21% oxygen before left liver lobe ischemia (45 min) and reperfusion (4 hr). The interactions of hypoxia→adenosine→adenosine receptors were tested by pharmacologic antagonism at adenosine receptor (AR) sites in wild-type mice and in mice with genetic deletions at the A1, A2A, A2B, and A3 ARs. Hepatocellular damage, inflammation, and metabolic effects were quantified by enzyme activities, cytokines, liver myeloperoxidase, blood adenosine, and tissue AMP, respectively.
resultsHepatoprotection by HPC was significant in wild-type and A1, A2A, and A3 AR knockout mice as quantified by lower alanine aminotransferase serum activities, cytokine levels, histologic damage scores, tissue myeloperoxidase concentrations, and preserved AMP concentrations. Protection by HPC was blunted in mice pretreated with the A2B AR antagonist MRS1754 or in A2B AR knockout mice.
conclusionsBecause liver protective effects of HPC are negated when the A2B receptor is nonfunctional, the hypoxia→adenosine→A2B receptor pathway plays a critical role in the prevention of warm IRI in vivo. Hypoxic activation of this pathway warrants use of selective A2B AR agonists or even intermittent hypoxia (e.g., in deceased organ donors) to protect from liver IRI.
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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.