Role of the intestinal tract in the elimination of uric acid

Sørensen, Leif

doi:10.1002/art.1780080429

Cited by 195 publications

(145 citation statements)

References 15 publications

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“…It has been suggested that one-third to one-fourth of uric acid is recovered in feces, indicating that biliary and/or intestinal secretion is an important alternative pathway(s) of uric acid excretion. 27) Recently, it has been reported that ABCG2, a member of the ATP-binding cassette transporter superfamily, plays a key role in the regulation of urate homeostasis. It is highly expressed on the renal proximal tubular cells, the apical membranes the intestinal epithelium and the liver hepatocytes, mediating the renal and/or extra-renal urate excretion, as a high-capacity urate exporter, 28,29) and its dysfunction has an association with serum uric acid levels and gout/hyperuricemia risk.…”

Section: Discussionmentioning

confidence: 99%

Mangiferin Inhibits Renal Urate Reabsorption by Modulating Urate Transporters in Experimental Hyperuricemia

Yang

Gao

Niu

et al. 2015

Biological & Pharmaceutical Bulletin

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Mangiferin, a natural glucosyl xanthone from the leaves of Mangifera indica L., was previously shown to exert potent hypouricemic effects associated with inhibition of the activity of xanthine dehydrogenase/ oxidase. The present study aimed to evaluate its uricosuric effect and possible molecular mechanisms underlying the renal urate transporters responsible for urate reabsorption in vivo. Mangiferin (1.5-24.0 mg/kg) was administered intragastrically to hyperuricemic mice and rats induced by the intraperitoneal injection of uric acid and potassium oxonate, respectively. The uricosuric effect was evaluated by determining the serum and urinary urate levels as well as fractional excretion of uric acid (FEUA). The mRNA and protein levels of renal urate-anion transporter 1 (URAT1), organic anion transporter 10 (OAT10), glucose transporter 9 (GLUT9), and PDZ domain-containing protein (PDZK1) were analyzed. The administration of mangiferin significantly decreased the serum urate levels in hyperuricemic mice in a dose-and time-dependent manner. In hyperuricemic rats, mangiferin also reduced the serum urate levels and increased the urinary urate levels and FEUA. These results indicate that mangiferin has uricosuric effects. Further examination showed that mangiferin markedly inhibited the mRNA and protein expression of renal URAT1, OAT10, and GLUT9 in hyperuricemic rats, but did not interfere with PDZK1 expression. Taken together, these findings suggest that mangiferin promotes urate excretion by the kidney, which may be related to the inhibition of urate reabsorption via downregulation of renal urate transporters.

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Section: Discussionmentioning

confidence: 99%

Mangiferin Inhibits Renal Urate Reabsorption by Modulating Urate Transporters in Experimental Hyperuricemia

Yang

Gao

Niu

et al. 2015

Biological & Pharmaceutical Bulletin

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“…UA is primarily formed in the liver. About two thirds of UA is excreted by the kidney, and the rest is eliminated by the gastrointestinal tract [1]. An increase in serum UA results from overproduction, impaired excretion, or combined mechanisms [2].…”

Section: Introductionmentioning

confidence: 99%

Serum Uric Acid and Endothelial Dysfunction in Continuous Ambulatory Peritoneal Dialysis Patients

Tang

Cheng

2008

Am J Nephrol

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Background: Endothelial dysfunction is an early predictor of cardiovascular events. Hyperuricemia has been shown to be associated with increased cardiovascular mortality. It remains unclear if serum uric acid (UA) is associated with endothelial dysfunction in peritoneal dialysis patients. Methods: In this cross-sectional study, the relationship of UA and endothelial dysfunction was investigated in 189 stable peritoneal dialysis patients. The clinical and laboratory data were collected. Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. Results: UA levels did not differ between 93 male and 96 female patients (416.31 ± 86.93 vs. 395.52 ± 87.47 μmol/l, p > 0.05). Patients were grouped into three tertiles on the basis of their serum UA levels. Systolic blood pressure (p = 0.007), serum phosphate (p = 0.005), high-sensitive C-reactive protein (hs-CRP) (p < 0.001), and FMD (p = 0.016) were all different among UA tertiles. FMD was found to be related with UA (p = 0.002) and hs-CRP (p = 0.006) in a Pearson’s correlation analysis. Multivariate regression analysis showed that only UA was an independent determinant of FMD (β = –0.237, p = 0.036). Conclusion: There was an independent correlation between UA and FMD, and a higher UA level was related to worse endothelial function which may contribute to hypertension and cardiovascular morbidity.

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“…Maintenance of some degree of plasma urate homeostasis in subjects with -chronic renal failure is achieved by an increase in both intestinal uricolysis (1) and absolute urate excretion per residual nephron (2,3). The role of each component of the tubular bidirectional transport system for urate at different stages of disease has been assessed with the pyrazinamide suppression test (3,4).…”

Section: Introductionmentioning

confidence: 99%

Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Boumendil-Podevin¹,

Podevin²,

Richet³

1975

J. Clin. Invest.

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A B S T R A C T Serum and urine from chronically uremic patients and normal individuals were subjected to gel filtration on Sephadex-G10. The effects of the eluted fractions on the uptake of urate and para-aminohippurate by isolated cortical tubules of rabbit kidney were investigated. According to the origin of the samples, one to three major groups of fractions inhibiting both urate and para-aminohippurate transport were disclosed. The first eluted group occurred for all the samples under study. The second one was demonstrated in both sera and urines from uremic patients but only in urines from normal individuals. The third one was exclusively detected in uremic sera and urines. Among all the compounds identified, only hippuric acid, eluted in the fractions of the second group, was capable of inhibiting the uptake of urate and para-aminohippurate in vitro. The concentration for which this inhibitory effect of hippuric acid occurred was in the range of that existing in uremic sera. Indoxyl sulfate, which accumulates to very high concentrations in uremic serum, could not be disclosed in the above-mentioned fractions. This is explained by the strong adsorption of this indole derivative to Sephadex gel. Potassium indoxyl sulfate, when tested in vitro at the concentration existing in uremic serum, substantially inhibited the uptake of both urate and para-aminohippurate. In normal subjects, ingestion of hippuric acid or potassium indoxyl sulfate significantly increased fractional urinary excretion of uric acid. On the basis of these results, it is suggested that progressive retention of hippuric acid, indoxyl sulfate, and other yet unidentified inhibitors may explain the gradual increase in urinary fractional excretion of urate This work was presented in part at a symposium on uremia sponsored by the International

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Role of the intestinal tract in the elimination of uric acid

Cited by 195 publications

References 15 publications

Mangiferin Inhibits Renal Urate Reabsorption by Modulating Urate Transporters in Experimental Hyperuricemia

Mangiferin Inhibits Renal Urate Reabsorption by Modulating Urate Transporters in Experimental Hyperuricemia

Serum Uric Acid and Endothelial Dysfunction in Continuous Ambulatory Peritoneal Dialysis Patients

Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

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