Uridine-5′-triphosphate Protects Against Hepatic- Ischemic/Reperfusion Injury in Mice

Ben‐Ari, Ziv; Pappo, Orit; Yitzhaki, Smadar; Cheporko, Yelena; Shainberg, Asher; Zinman, Tova; Ravid, Amiram; Zemel, Romi; Bachmatov, Larisa; Kurtzwald, Efrat; Mor, Eytan; Hochhauser, Edith

doi:10.1097/tp.0b013e31819e3cdc

Cited by 6 publications

(5 citation statements)

References 34 publications

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“…I/R injury induces ER stress by modulating liver inflammatory immune response in experimental animal models [23] and by initiating cell death mechanisms. We have demonstrated in a previous study that ATP deficiency caused by hypoxia can promote escape of Ca 2+ from ER into cytosol, triggering several downstream pathways that promote cell death [24]. One of the components of the ER stress-mediated apoptosis pathway is C/EBP homologous protein (CHOP), also known as growth arrest- and DNA damage-inducible gene 153 (GADD153) [25].…”

Section: Discussionmentioning

confidence: 99%

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury

et al. 2013

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Ischemia/reperfusion (I/R) injury is the main cause of primary graft dysfunction of liver allografts. Cobalt-protoporphyrin (CoPP)–dependent induction of heme oxygenase (HO)-1 has been shown to protect the liver from I/R injury. This study analyzes the apoptotic mechanisms of HO-1-mediated cytoprotection in mouse liver exposed to I/R injury. HO-1 induction was achieved by the administration of CoPP (1.5 mg/kg body weight i.p.). Mice were studied in in vivo model of hepatic segmental (70 %) ischemia for 60 min and reperfusion injury. Mice were randomly allocated to four main experimental groups (n = 10 each): (1) A control group undergoing sham operation. (2) Similar to group 1 but with the administration of CoPP 72 h before the operation. (3) Mice undergoing in vivo hepatic I/R. (4) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction. When compared with the I/R mice group, in the I/R+CoPP mice group, the increased hepatic expression of HO-1 was associated with a significant reduction in liver enzyme levels, fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase-3, there was a decreased mean number of proliferating cells (positively stained for Ki67), and a reduced hepatic expression of: C/EBP homologous protein (an index of endoplasmic reticulum stress), the NF-κB’s regulated genes (CIAP2, MCP-1 and IL-6), and increased hepatic expression of IκBa (the inhibitory protein of NF-κB). HO-1 over-expression plays a pivotal role in reducing the hepatic apoptotic IR injury. HO-1 may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation.

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Section: Discussionmentioning

confidence: 99%

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury

et al. 2013

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“…Multiple modalities have been available to alleviate additional reperfusion injuries, primarily including ischemic preconditioning and the use of preservation fluid and cytoprotective agents [7][8][9][10]. In our previous study, hemi-hepatic artery-preserved portal occlusion caused less severe reperfusion injury, both biochemically and pathologically, than the Pringle's maneuver; the underlying mechanism is, however, less understood [11].…”

Section: Introductionmentioning

confidence: 94%

Attenuation of Reperfusion-Induced Hepatocyte Apoptosis is Associated with Reversed bcl-2/bax Ratio in Hemi-Hepatic Artery-Preserved Portal Occlusion

Jin

Dai

2012

Journal of Surgical Research

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“…Resistance of hepatocytes to hypoxia is promoted by P2Y 2 R. In mice, CD39 deletion from natural killer (NK) cells reduced hepatic ischaemia/reperfusion injury, indicating that during liver regeneration ATP modulates NK cell function. UTP acting via P2Y 2 and/or P2Y 4 R before induction of ischaemia attenuates post-ischaemic hepatocyte apoptosis resulting in a reduction of liver damage ( Ben-Ari et al, 2009 ). Platelet aggregation triggered by ADP may have a role in ischaemia reperfusion injury ( Schulte am Esch et al, 2010 ).…”

Section: Diseases Of the Livermentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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Uridine-5′-triphosphate Protects Against Hepatic- Ischemic/Reperfusion Injury in Mice

Cited by 6 publications

References 34 publications

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury

Attenuation of Reperfusion-Induced Hepatocyte Apoptosis is Associated with Reversed bcl-2/bax Ratio in Hemi-Hepatic Artery-Preserved Portal Occlusion

Purinergic Signalling: Therapeutic Developments

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