Excess activation of circulating
xanthine oxidoreductase (XOR) may contribute to the pathogenesis of widespread remote organ injury, including kidney injury. The purpose of this study was to determine the acute impact of marathon running on plasma XOR activity and to examine whether plasma XOR activity is associated with marathon-induced elevations in
biomarkers of
acute kidney injury (AKI). Twenty-three young men (aged 20-25 yr) who participated in the 38th Tsukuba Marathon were included. Blood and urine samples were collected before, immediately, 2 h (only blood sample), and 24 h after a full marathon run. Plasma XOR activity was evaluated using a highly sensitive assay utilizing a combination of [13C2,15N2]
xanthine and liquid chromatography-triple quadrupole mass spectrometry. The levels of several AKI
biomarkers, such as serum
creatinine and urinary liver-type
fatty acid-binding protein (L-FABP) were measured in each participant. Marathon running caused a transient elevation in plasma XOR activity and levels of
purine degradation products (
hypoxanthine,
xanthine, and
uric acid) as well as serum
creatinine, urinary
albumin, and urinary L-FABP levels. Immediately after the marathon, individual relative changes in plasma XOR activity were independently correlated with corresponding changes in serum
creatinine and urinary L-FABP levels. In addition, the magnitude of marathon-induced elevation in plasma XOR activity and levels of
purine degradation products were higher in individuals who developed AKI. These findings collectively suggest that marathon running substantially influences the
purine metabolism pathway including XOR activity. Moreover, activated circulating XOR can be partly associated with elevated
biomarkers of AKI after marathon running.NEW & NOTEWORTHY This study is the first to show marathon running transiently increases plasma XOR activity and levels of
purine degradation products (
hypoxanthine,
xanthine, and
uric acid), and further to demonstrate that activated plasma XOR may contribute to marathon-induced elevations in
biomarkers of AKI. These findings significantly extend our prior knowledge of the
purine metabolic pathway and several AKI
biomarkers under strenuous exercise conditions.