• Modeling Mechanism：

  ① Potassium oxonate, as a selective competitive inhibitor of uricase, blocks the activity of hepatic uricase, inhibits uric acid catabolism, and leads to the accumulation of uric acid in the body; ② Adenine, as a purine precursor, increases uric acid production and synergistically increases serum uric acid (UA) levels with potassium oxalate; ③ Persistent hyperuricemia leads to dysfunction of renal uric acid transporters (upregulation of reabsorption transporters and downregulation of secretory transporters), which in turn leads to renal tubular damage and inflammatory infiltration, mimicking the pathophysiological process of human hyperuricemia and related kidney damage.

• Related Products：

  Potassium oxonate (T5987)

• Modeling Method：

  Experimental Subject：

  Mice: Kunming strain, male, 7 weeks old, weighing approximately 20–25 g

  Dosage and Administration Route：

  ① Core modelling: Potassium oxalate (200 mg/kg)+Adenine (50 mg/kg), Suspended in 5% arabic gum solution, Oral gavage administration;
  ② Control treatment: Equal volume of 5% arabic gum solution; administered via the same gavage method;
  ③ Intervention validation (optional): Phenylbromomalonate (50 mg/kg), Suspended in 5% arabic gum solution, Administered via gastric lavage, Administered 1 hour after modelling drugs, for 21 consecutive days.

  Dosing Frequency and Duration Model：

  Once daily, for 21 consecutive days

• Validation：

  Serum uric acid (UA): Significantly increased on day 3 of modeling (model group 123.45 μmol/L vs control group 42.03 μmol/L, p<0.001), peaking on day 7 (approximately 175.70 μmol/L, 3 times that of the control group), and then remained stable at a high level; Uric acid clearance (Cur): Significantly decreased from day 3 (model group 0.73 vs control group 1.56), and continued to decrease with the extension of modeling time (decreased to 0.19 on day 21); Urine indicators: The 24-hour urine volume of the model group was significantly increased, but the urinary uric acid excretion was reduced; Pathological indicators: - HE staining: Mild renal tubular epithelial cell necrosis and inflammatory infiltration appeared on day 3; the damage worsened from day 10, manifested as renal tubular dilation, blurred cell boundaries, and a large number of inflammatory cell infiltrations, with amyloid bodies visible in some renal tubules; Molecular indicators: - Renal transporters: Western blot detection showed that on day 3 of modeling... From day 7 onwards, the expression of URAT1 and GLUT9 (uric acid reabsorption transporters) proteins was significantly upregulated, while the expression of ABCG2 and OAT1 (uric acid secretion transporters) was significantly downregulated. NPT1 (secretion transporter) was significantly downregulated from day 7, with the most significant change on day 10. General condition: - Mice in the model group were lethargic, had decreased weight, dry fur, increased water intake and decreased food intake, which were significantly different from the normal group.

*Precautions： On days 3, 7, 10, 14, 17, and 21 after blood collection, these mice were subsequently euthanized by carbon dioxide.

*References：Wen S,et,al. 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.