Xanthine oxidoreductase activity in marathon runners: potential implications for marathon-induced acute kidney injury
Xanthine oxidoreductase activity in marathon runners: potential implications for marathon-induced acute kidney injury
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马拉松运动员的黄嘌呤氧化还原酶活性：对马拉松诱发的急性肾损伤的潜在影响
DOI：
10.1152/japplphysiol.00669.2021
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发表时间：
2022
影响因子：
3.3
通讯作者：
Maeda Seiji
中科院分区：
文献类型：
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作者：
Kosaki Keisei;Kumamoto Shota;Tokinoya Katsuyuki;Yoshida Yasuko;Sugaya Takeshi;Murase Takayo;Akari Seigo;Nakamura Takashi;Nabekura Yoshiharu;Takekoshi Kazuhiro;Maeda Seiji
循环黄嘌呤氧化还原酶（XOR）的过度激活可能导致广泛的远端器官损伤，包括肾损伤的发病机制。本研究的目的是确定马拉松跑步对血浆XOR活性的急性影响，并检查血浆XOR活性是否与马拉松诱导的急性肾损伤（阿基）生物标志物升高相关。参加第38届筑波马拉松的23名年轻男子（年龄20-25岁）被纳入。在全程马拉松跑前、跑后即刻、跑后2 h（仅采集血样）和跑后24 h采集血样和尿样。使用高灵敏度的测定，利用[13 C2，15 N2]黄嘌呤和液相色谱-三重四极杆质谱法的组合，血浆XOR活性进行了评价。在每位参与者中测量了几种阿基生物标志物的水平，如血清肌酐和尿肝型脂肪酸结合蛋白（L-FABP）。马拉松跑引起血浆XOR活性和嘌呤降解产物（次黄嘌呤、黄嘌呤和尿酸）水平以及血清肌酐、尿白蛋白和尿L-FABP水平的短暂升高。马拉松后，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，在发生阿基的个体中，马拉松引起的血浆XOR活性和嘌呤降解产物水平升高的幅度更高。这些研究结果共同表明，马拉松跑实质上影响嘌呤代谢途径，包括XOR活性。此外，激活的循环XOR可能与马拉松跑步后阿基的生物标志物升高部分相关。新&值得注意的是，这项研究首次表明，马拉松跑步短暂增加血浆XOR活性和嘌呤降解产物（次黄嘌呤，黄嘌呤和尿酸）的水平，并进一步证明激活的血浆XOR可能有助于马拉松诱导的阿基生物标志物升高。这些发现显著扩展了我们先前对剧烈运动条件下嘌呤代谢途径和几种阿基生物标志物的了解。
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 & NOTEWORTHYThis 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.