Boardman 2019 Can J Physiol Pharmacol

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Boardman NT, Falck AT, Lund T, Chu X, Martin-Armas M, Norvik JV, Jenssen TG, Ytrehus K (2019) Human concentrations of uric acid scavenges adaptive and maladaptive ROS in isolated rat hearts subjected to ischemic stress. Can J Physiol Pharmacol [Epub ahead of print].

» PMID: 31518503

Boardman NT, Falck AT, Lund T, Chu X, Martin-Armas M, Norvik JV, Jenssen TG, Ytrehus K (2019) Can J Physiol Pharmacol

Abstract: Uric acid is a purine degradation product but also an important antioxidant and ROS scavenger. Experimental settings that mimic myocardial ischemia-reperfusion have not included uric acid despite that it is always present in human extracellular fluid and plasma. We hypothesized that uric acid has an important role in myocardial ROS scavenging. Here, we tested the cardiac response to uric acid on infarct size following ischemia-reperfusion with and without exacerbated oxidative stress due to acute pressure overload and during preconditioning. We also examined mitochondrial respiration and ROS-induced mitochondrial permeability transition pore opening. Under exacerbated ROS stress induced by high pressure perfusion, uric acid lowered oxidative stress and reduced infarct size. In contrast, uric acid blocked cardioprotection induced by ischemic preconditioning. However, this effect was reversed by probenecid, an inhibitor of cellular uptake of uric acid. In accordance, in intact cardiomyocytes, extracellular uric acid reduced the susceptibility of mitochondria towards opening of the permeability transition pore, suggesting that uric acid may prevent ischemia-reperfusion injury due to scavenging of maladaptive ROS. Moreover, as uric acid also scavenges also adaptive ROS, this may interfere with preconditioning. Altogether, uric acid might be a confounder when translating preclinical experimental results into clinical treatment.

Keywords: Uric acid, ROS, Cardioprotection, Ischemic pre-conditioning, Pressure overload/high pressure Bioblast editor: Plangger M O2k-Network Lab: NO Tromsoe Larsen TS


Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Ischemia-reperfusion, Oxidative stress;RONS  Organism: Rat  Tissue;cell: Heart  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k 

Labels, 2019-10