A historical journey of searching for uricosuric drugs

Jansen, Tim; Giesen, Tanja; Janssen, Matthijs

doi:10.1007/s10067-021-05930-1

Cited by 15 publications

(11 citation statements)

References 47 publications

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“…45 Increasing UA excretion is another strategy for treating HUA. [46][47][48] Previous studies found that various natural products are efficient in lowering the blood UA concentration via regulating UA transporters. 49,50 GLUT9 functions as a major UA reabsorption transporter in the kidneys, 51 and is down-regulated by GLPP.…”

Section: Papermentioning

confidence: 99%

Ganoderma lucidumpolysaccharide peptide alleviates hyperuricemia by regulating adenosine deaminase and urate transporters

Lin

Meng

et al. 2022

Food Funct.

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Section: Papermentioning

confidence: 99%

Ganoderma lucidumpolysaccharide peptide alleviates hyperuricemia by regulating adenosine deaminase and urate transporters

Lin

Meng

et al. 2022

Food Funct.

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“…Considering the protective effect of OAT10 dysfunction on gout susceptibility (OR = 0.67) ( Higashino et al, 2020 ), in the context of the potentially simultaneous inhibition of renal URAT1 and OAT10 ( Figure 6 ), it would be interesting to determine whether lesinurad, which had been an approved uricosuric agent that was recently withdrawn from the market unfortunately because of low market penetration, not because of therapeutic issues ( Jansen et al, 2022 ), could have an anti-gout effect stronger than other uricosuric agents that inhibit only URAT1 in clinical situations. It is possible that the positive effects of OAT10 dysfunction may depend on OAT10 expressed not only in the kidney but also in other tissues; such a notion should be addressed in future clinical studies.…”

Section: Discussionmentioning

confidence: 99%

OAT10/SLC22A13 Acts as a Renal Urate Re-Absorber: Clinico-Genetic and Functional Analyses With Pharmacological Impacts

et al. 2022

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Dysfunctional missense variant of organic anion transporter 10 (OAT10/SLC22A13), rs117371763 (c.1129C>T; p.R377C), is associated with a lower susceptibility to gout. OAT10 is a urate transporter; however, its physiological role in urate handling remains unclear. We hypothesized that OAT10 could be a renal urate re-absorber that will be a new molecular target of urate-lowering therapy like urate transporter 1 (URAT1, a physiologically-important well-known renal urate re-absorber) and aimed to examine the effect of OAT10 dysfunction on renal urate handling. For this purpose, we conducted quantitative trait locus analyses of serum urate and fractional excretion of uric acid (FEUA) using samples obtained from 4,521 Japanese males. Moreover, we performed immunohistochemical and functional analyses to assess the molecular properties of OAT10 as a renal urate transporter and evaluated its potential interaction with urate-lowering drugs. Clinico-genetic analyses revealed that carriers with the dysfunctional OAT10 variant exhibited significantly lower serum urate levels and higher FEUA values than the non-carriers, indicating that dysfunction of OAT10 increases renal urate excretion. Given the results of functional assays and immunohistochemical analysis demonstrating the expression of human OAT10 in the apical side of renal proximal tubular cells, our data indicate that OAT10 is involved in the renal urate reabsorption in renal proximal tubules from urine. Additionally, we found that renal OAT10 inhibition might be involved in the urate-lowering effect of losartan and lesinurad which exhibit uricosuric effects; indeed, losartan, an approved drug, inhibits OAT10 more strongly than URAT1. Accordingly, OAT10 can be a novel potential molecular target for urate-lowering therapy.

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“…), and uricosuric agents (benzbromarone, etc.) show great effectiveness but are associated with harmful side effects, including impairment of liver function or injury [ 11 , 12 , 13 ]. Some natural products, including chicory, green alga Enteromorpha prolifera polysaccharide, and fucoidan, have been described in the literature to have excellent anti-hyperuricemia effects with hardly any toxicity [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Ameliorative Effect of Mannuronate Oligosaccharides on Hyperuricemic Mice via Promoting Uric Acid Excretion and Modulating Gut Microbiota

et al. 2023

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Mannuronate oligosaccharide (MOS) is α-D-mannuronic acid polymer with 1,4-glycosidic linkages that possesses beneficial biological properties. The aim of this study was to investigate the hypouricemic effect of MOS in hyperuricemic mice and demonstrate the possible protective mechanisms involved. In this research, 200 mg/kg/day of MOS was orally administered to hyperuricemic mice for four weeks. The results showed that the MOS treatment significantly reduced the serum uric acid (SUA) level from 176.4 ± 7.9 μmol/L to 135.7 ± 10.9 μmol/L (p < 0.05). MOS alleviated the inflammatory response in the kidney. Moreover, MOS promoted uric acid excretion by regulating the protein levels of renal GLUT9, URAT1 and intestinal GLUT9, ABCG2. MOS modulated the gut microbiota in hyperuricemic mice and decreased the levels of Tyzzerella. In addition, research using antibiotic-induced pseudo-sterile mice demonstrated that the gut microbiota played a crucial role in reducing elevated serum uric acid of MOS in mice. In conclusion, MOS may be a potential candidate for alleviating HUA symptoms and regulating gut microbiota.

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A historical journey of searching for uricosuric drugs

Cited by 15 publications

References 47 publications

Ganoderma lucidumpolysaccharide peptide alleviates hyperuricemia by regulating adenosine deaminase and urate transporters

Ganoderma lucidumpolysaccharide peptide alleviates hyperuricemia by regulating adenosine deaminase and urate transporters

OAT10/SLC22A13 Acts as a Renal Urate Re-Absorber: Clinico-Genetic and Functional Analyses With Pharmacological Impacts

Ameliorative Effect of Mannuronate Oligosaccharides on Hyperuricemic Mice via Promoting Uric Acid Excretion and Modulating Gut Microbiota

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