Electrochemical analysis of uric acid excretion to the intestinal lumen: Effect of serum uric acid-lowering drugs and 5/6 nephrectomy on intestinal uric acid levels
Electrochemical analysis of uric acid excretion to the intestinal lumen: Effect of serum uric acid-lowering drugs and 5/6 nephrectomy on intestinal uric acid levels
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DOI：
10.1371/journal.pone.0226918
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发表时间：
2019-12-31
期刊：
影响因子：
3.7
通讯作者：
Ichida, Kimiyoshi
中科院分区：
文献类型：
--
作者：
Fujita, Kyoko;Yamada, Hiroki;Ichida, Kimiyoshi
近年来，人们对肾外尿酸（UA）排泄途径的重要性及其在UA相关疾病中的作用进行了广泛的研究。然而，通常用于测量肠腔中UA浓度的方法难以进行真实的实时和动态分析。在这项研究中，尿酸排泄在大鼠肠腔中的真实的时间使用电化学方法进行了测量。利用混合自组装膜修饰金电极，构建了检测尿酸的敏感电极。利用时间过程数据计算UA在肠道中的排泄率。给予血清UA降低药物（苯溴马隆、非布司他和托吡司他）后，在肠道中观察到UA排泄率降低。这些药物可抑制ATP结合盒转运体G2（ABCG 2），ABCG 2已被报道为UA的重要输出者。另一方面，在5/6肾切除大鼠的肠道中观察到尿酸排泄率增加。UA转运体有机阴离子转运体OAT 3的mRNA表达上调，这与基膜的分泌有关，表明ABCG 2（一种高容量UA输出者）增强了UA排泄。观察尿酸排泄动力学和尿酸转运蛋白的mRNA表达在肠道管理血清尿酸降低药物和5/6肾切除术后，提高我们的理解肠道尿酸排泄的潜在机制。
Recently, extensive efforts have been made to understand the importance of the extra-renal uric acid (UA) excretion pathways and their contribution to UA-related diseases. However, the method typically used to measure UA concentrations in the intestinal lumen is difficult to real time and dynamic analysis. In this study, UA excretion in the rat intestinal lumen was measured in real time using an electrochemical method. A sensitive electrode to detect UA was constructed using a gold electrode modified with a mixed self-assembled monolayer. Excretion rate of UA in the intestine was calculated using time course data. A decrease in UA excretion rate was observed in the intestine after administration of serum UA-lowering drugs (benzbromarone, febuxostat, and topiroxostat). Inhibition of ATP-binding cassette transporter G2 (ABCG2) which has been reported as an important exporter of UA was suggested by administration of these drugs. On the other hand, an increase in excretion rate of UA was observed in the intestine of 5/6 nephrectomy rats. Upregulation of mRNA expression of the UA transporter organic anion transporter OAT3, which is related to the secretion at the basal membrane, suggested an enhancement of UA excretion by ABCG2, a high-capacity UA exporter. Observed urate excretion dynamics and mRNA expression of UA transporters in the intestine upon administration of serum UA-lowering drugs and 5/6 nephrectomy improve our understanding of the underlying mechanisms of intestinal UA excretion.