Olsalazine Sodium Increases Renal Urate Excretion by Modulating Urate Transporters in Hyperuricemic Animals.
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Niu Y, Yang P, Li H, Li Q, Lin H, Gao L, Li L
Olsalazine Sodium Increases Renal Urate Excretion by Modulating Urate Transporters in Hyperuricemic Animals.
Biol Pharm Bull. 2020 Nov 1;43(11):1653-1659. doi: 10.1248/bpb.b20-00362. Epub 2020 Aug 28.
- PubMed ID
- 32863294 [ View in PubMed]
- Abstract
Hyperuricemia is mainly the result of relative underexcretion of urate. Urate is mainly eliminated by kidney and several important transporters expressed on the membrane of renal tubular cells involved in urate excretion. Olsalazine sodium was screened from 3167 authorized small compounds/drugs, targeting xanthine oxidoreductase. In previous study, we reported that olsalazine sodium significantly reduced the serum urate levels, and the anti-hyperuricemic activity linked with inhibiting urate formation by reducing the activity of xanthine oxidoreductase. The current research aimed to assess olsalazine sodium renal urate excretion and likely molecular mechanism. The results showed that administration of olsalazine sodium 5.0 mg/kg decreased the levels of serum urate in hyperuricemic rats, and noticeably improved the fractional excretion of urate and urate clearance, exhibiting an uricosuric action. Moreover, olsalazine sodium (2.5, 5.0, 10.0 mg/kg) reduced the level of blood urea nitrogen in rats. Further study showed that olsalazine sodium reduced the mRNA expression of urate reabsorptive transporter glucose transporter 9 (GLUT9), increased the mRNA expression of urate secretory transporters, organic anion transporter 1 (OAT1), OAT3 and type 1 sodium-dependent phosphate transporter (NPT1) as well as the protein expression of OAT3 in the kidney in hyperuricemic mice. In conclusion, olsalazine sodium exhibited a promotion of urate excretion in kidney by increasing the expression of OAT3.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Olsalazine Sodium-dependent phosphate transporter 1 Protein Humans UnknownUpregulatorDetails Olsalazine Solute carrier family 2, facilitated glucose transporter member 9 Protein Humans UnknownDownregulatorDetails Olsalazine Solute carrier family 22 member 6 Protein Humans UnknownUpregulatorDetails Olsalazine Solute carrier family 22 member 8 Protein Humans UnknownUpregulatorDetails