TY - JOUR
T1 - Xanthine oxidoreductase activity in marathon runners
T2 - potential implications for marathon-induced acute kidney injury
AU - Kosaki, Keisei
AU - Kumamoto, Shota
AU - Tokinoya, Katsuyuki
AU - Yoshida, Yasuko
AU - Sugaya, Takeshi
AU - Murase, Takayo
AU - Akari, Seigo
AU - Nakamura, Takashi
AU - Nabekura, Yoshiharu
AU - Takekoshi, Kazuhiro
AU - Maeda, Seiji
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research KAKENHI from the Ministry of Education, Culture, Sports, Science, and Technology, Japan under Grant Nos. 19K22796 and 22K17730.
Publisher Copyright:
8750-7587/22 Copyright © 2022 the American Physiological Society.
PY - 2022/7
Y1 - 2022/7
N2 - 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 [13C215N2] 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.
AB - 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 [13C215N2] 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.
KW - kidney damage
KW - liver-type fatty acid-binding protein
KW - marathon running
KW - purine metabolism
KW - strenuous exercise
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U2 - 10.1152/japplphysiol.00669.2021
DO - 10.1152/japplphysiol.00669.2021
M3 - Article
C2 - 35608201
AN - SCOPUS:85133009672
VL - 133
SP - 1
EP - 10
JO - Journal of Applied Physiology Respiratory Environmental and Exercise Physiology
JF - Journal of Applied Physiology Respiratory Environmental and Exercise Physiology
SN - 8750-7587
IS - 1
ER -