Abstract
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.
Highlights
Uric acid (UA) is the end product of purine metabolism in humans
Gold bead electrodes modified with mixed self-assembled monolayers (SAM) were set in the integrated device and current change based on UA concentration was measured in Cyclic voltammetry (CV) and amperometry
Mixed SAM modified with HS-C6-Fc: HS-C6-OH = 1:3 showed the highest sensitivity of UA detection compared with SAM modified with HS-C6-Fc:HS-C6-OH = 1:1 and 3:1
Summary
Uric acid (UA) is the end product of purine metabolism in humans. Serum UA levels are determined by the balance between UA production and UA excretion rates. High serum UA levels, which are considered to be higher than 7 mg/dL, are diagnosed as hyperuricemia This condition induces gout and accelerates the progression of renal and cardiovascular diseases [1,2,3]. Vaziri and colleagues showed an increase in intestinal UA excretion in a rat model of chronic kidney disease, in which renal UA excretion is greatly impaired [13]. The impact of the urate transporter ABCG2 function in the intestine on the levels of serum UA has been reported. Yano and colleagues showed that 5/6 nephrectomized rats exhibited lower excretion of UA in the urine and overexpression of ABCG2 in the ileum, while serum UA did not significantly increase [14]. The effect of serum UA-lowering drugs on the urate transport activity of ABCG2 has been reported [16]. A dynamic analysis of UA concentration in the rat intestine at steady state and after administration of different serum UA-lowering drugs or 5/6 nephrectomy was performed
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