We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Human concentrations of uric acid scavenges adaptive and maladaptive reactive oxygen species in isolated rat hearts subjected to ischemic stress.
- Authors
Boardman, Neoma T.; Falck, Aleksander Tank; Lund, Trine; Chu, Xi; Martin-Armas, Montserrat; Norvik, Jon V.; Jenssen, Trond G.; Ytrehus, Kirsti
- Abstract
Uric acid is a purine degradation product but also an important antioxidant and reactive oxygen species (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 adaptive ROS, this may interfere with preconditioning. Altogether, uric acid might be a confounder when translating preclinical experimental results into clinical treatment.
- Subjects
URIC acid; REACTIVE oxygen species; MYOCARDIAL reperfusion; EXTRACELLULAR fluid; ISCHEMIC preconditioning; OXIDATIVE stress
- Publication
Canadian Journal of Physiology & Pharmacology, 2020, Vol 98, Issue 3, p139
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2019-0024