Olsalazine Sodium Increases Renal Urate Excretion by Modulating Urate Transporters in Hyperuricemic Animals

Autor: Yanfen Niu, Hongjian Li, Ling Li, Hua Lin, Pingfen Yang, Lihui Gao, Li Qiang
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Uricosuric
Monosaccharide Transport Proteins
Glucose Transport Proteins
Facilitative
Pharmaceutical Science
Hyperuricemia
Organic Anion Transporters
Sodium-Independent
Blood Urea Nitrogen
Excretion
Kidney Tubules
Proximal
Rats
Sprague-Dawley
03 medical and health sciences
Mice
0302 clinical medicine
Organic Anion Transport Protein 1
Internal medicine
medicine
Animals
Humans
Olsalazine Sodium
Urate excretion
Blood urea nitrogen
Pharmacology
Kidney
Dose-Response Relationship
Drug
Chemistry
Transporter
General Medicine
medicine.disease
Renal Reabsorption
Rats
Uric Acid
Aminosalicylic Acids
Disease Models
Animal
Renal Elimination
030104 developmental biology
medicine.anatomical_structure
Endocrinology
030220 oncology & carcinogenesis
Creatinine
Sodium-Phosphate Cotransporter Proteins
Type I
Zdroj: Biologicalpharmaceutical bulletin. 43(11)
ISSN: 1347-5215
Popis: 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.
Databáze: OpenAIRE
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