Faculty of Health and Sport Sciences, University of Tsukuba, Ibaraki, Japan.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
J Appl Physiol (1985). 2022 Jul 1;133(1):1-10. doi: 10.1152/japplphysiol.00669.2021. Epub 2022 May 19.
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 [C,N] 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. 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.
循环黄嘌呤氧化还原酶（XOR）的过度激活可能导致广泛的远处器官损伤的发病机制，包括肾脏损伤。本研究旨在确定马拉松跑步对血浆 XOR 活性的急性影响，并研究血浆 XOR 活性是否与马拉松引起的急性肾损伤（AKI）生物标志物升高有关。纳入了 23 名参加第 38 届筑波马拉松的年轻男性（年龄 20-25 岁）。在全马跑后，收集了血液和尿液样本，分别在跑前、即刻、2 小时（仅收集血液样本）和 24 小时后进行。利用[C，N]黄嘌呤和液相色谱-三重四极杆质谱联用的高灵敏度测定法评估血浆 XOR 活性。测量了每个参与者的几种 AKI 生物标志物的水平，如血清肌酐和尿肝型脂肪酸结合蛋白（L-FABP）。马拉松跑步导致血浆 XOR 活性和嘌呤降解产物（次黄嘌呤、黄嘌呤和尿酸）以及血清肌酐、尿白蛋白和尿 L-FABP 水平的短暂升高。马拉松后即刻，血浆 XOR 活性的个体相对变化与血清肌酐和尿 L-FABP 水平的相应变化独立相关。此外，在发生 AKI 的个体中，马拉松引起的血浆 XOR 活性和嘌呤降解产物升高的幅度更大。这些发现共同表明，马拉松跑步极大地影响了包括 XOR 活性在内的嘌呤代谢途径。此外，循环激活的 XOR 可能与马拉松后 AKI 的生物标志物升高部分相关。本研究首次表明，马拉松跑步会短暂增加血浆 XOR 活性和嘌呤降解产物（次黄嘌呤、黄嘌呤和尿酸）的水平，并进一步表明激活的血浆 XOR 可能导致马拉松引起的 AKI 生物标志物升高。这些发现大大扩展了我们对剧烈运动条件下嘌呤代谢途径和几种 AKI 生物标志物的先前知识。
