The Time-Feature of Uric Acid Excretion in Hyperuricemia Mice Induced by Potassium Oxonate and Adenine

Int J Mol Sci. 2020 Jul 22;21(15):5178. doi: 10.3390/ijms21155178.

Abstract

Hyperuricemia is an important risk factor of chronic kidney disease, metabolic syndrome and cardiovascular disease. We aimed to assess the time-feature relationship of hyperuricemia mouse model on uric acid excretion and renal function. A hyperuricemia mouse model was established by potassium oxonate (PO) and adenine for 21 days. Ultra Performance Liquid Chromatography was used to determine plasma uric acid level. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and Western blot was used to detect renal urate transporters' expression. In hyperuricemia mice, plasma uric acid level increased significantly from the 3rd day, and tended to be stable from the 7th day, and the clearance rate of uric acid decreased greatly from the 3rd day. Further study found that the renal organ of hyperuricemia mice showed slight damage from the 3rd day, and significantly deteriorated renal function from the 10th day. In addition, the expression levels of GLUT9 and URAT1 were upregulated from the 3rd day, while ABCG2 and OAT1 were downregulated from the 3rd day, and NPT1 were downregulated from the 7th day in hyperuricemia mice kidney. This paper presents a method suitable for experimental hyperuricemia mouse model, and shows the time-feature of each index in a hyperuricemia mice model.

Keywords: hyperuricemia; mouse model; renal injury; urate transporter; uric acid excretion.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / blood
  • Adenine / toxicity
  • Animals
  • Chromatography, High Pressure Liquid
  • Creatinine / blood
  • Disease Models, Animal*
  • Glucose Transport Proteins, Facilitative / blood
  • Hyperuricemia / blood*
  • Hyperuricemia / chemically induced
  • Hyperuricemia / metabolism
  • Hyperuricemia / physiopathology*
  • Kidney / metabolism
  • Kidney / pathology*
  • Mice
  • Organic Anion Transport Protein 1 / blood
  • Organic Anion Transporters / blood
  • Organic Anion Transporters / metabolism
  • Oxonic Acid / toxicity
  • Sodium-Phosphate Cotransporter Proteins, Type I / blood
  • Time Factors
  • Uric Acid / blood*

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Abcg2 protein, mouse
  • Glucose Transport Proteins, Facilitative
  • Organic Anion Transport Protein 1
  • Organic Anion Transporters
  • Slc17a1 protein, mouse
  • Slc22a12 protein, mouse
  • Slc22a6 protein, mouse
  • Slc2a9 protein, mouse
  • Sodium-Phosphate Cotransporter Proteins, Type I
  • urate transporter
  • Uric Acid
  • potassium oxonate
  • Oxonic Acid
  • Creatinine
  • Adenine