Human concentrations of uric acid scavenges adaptive and maladaptive ROS in isolated rat hearts subjected to ischemic stress.

Human concentrations of uric acid scavenges adaptive and maladaptive ROS in isolated rat hearts subjected to ischemic stress. Can J Physiol Pharmacol. 2019 Sep 13;: Authors: Boardman NT, Falck AT, Lund T, Chu X, Martin-Armas M, Norvik JV, Jenssen TG, Ytrehus K 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 in...
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research