Human concentrations of uric acid scavenges adaptive and maladaptive reactive oxygen species in isolated rat hearts subjected to ischemic stress

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.

Distinct Prognostic Role of Serum Uric Acid Levels for Predicting All-Cause Mortality Among Chinese Adults Aged 45~75 Years With and Without Diabetes

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The mechanoreceptor DEG‐1 regulates cold tolerance in Caenorhabditis elegans

“…XDH acts enzymatically in the purine base salvage pathway and induces oxidative stress in the process of uric acid production [29,38]. However, uric acid functions as a potent antioxidant and protects against oxidative damage [39]. These findings suggest that the loss of XDH causes decreased ROS directly or increased ROS indirectly.…”

Sesamol Protects Testis from Ischemia-Reperfusion Injury through Scavenging Reactive Oxygen Species and Upregulating CREMτ Expression

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