• Modeling Mechanism：

  Inosine, a key precursor in purine metabolism, induces hyperuricemia through a core pathway: ① It is catalyzed by hepatic purine nucleoside phosphorylase (PNP) to produce hypoxanthine, which is then converted into uric acid by xanthine oxidase (XO). Excessive inosine intake disrupts the balance between uric acid production and excretion; ② It upregulates hepatic PNP mRNA expression while downregulating XO mRNA and protein expression (possibly as a compensatory inhibition of excessive uric acid production); ③ It does not affect the mRNA and protein expression of renal uric acid transporters (URAT1, OAT4, ABCG2, etc.). The core pathology is increased uric acid production, consistent with the mechanism of some subtypes of primary hyperuricemia in humans.

• Related Products：

  Inosine (T0437)

• Modeling Method：

  Experimental Subject：

  Rhesus macaque, Macaca mulatta, Male, 9–12 years old, Housed singly post-acclimatisation

  Dosage and Administration Route：

  ① Core modelling: Inosine, 200 mg/kg, dissolved in 0.9% saline, intraperitoneal injection, single-dose administration;
  ② Dose gradient validation: Three groups at 75 mg/kg, 100 mg/kg, and 200 mg/kg to identify optimal modelling dose;
  ③ Control treatment: Equal volume saline solution administered via intraperitoneal injection using the same method;
  ④ Model validation (optional):
  - Uric acid synthesis inhibitor intervention: Allopurinol (2.5 mg/kg), Febuxostat (2 mg/kg), Urodiol (2 mg/kg) administered intraperitoneally as required following inosine dosing;

  Dosing Frequency and Duration Model：

  Single dose

• Validation：

  Key indicators (serum uric acid, SUA): - 30 minutes after modeling, SUA levels increased from baseline 51.77±14.48 μmol/L to 178.32±14.47 μmol/L, peaking at 201.41±42.73 μmol/L at 1 hour (p<0.01), gradually declining after 4 hours, and approaching baseline at 8 hours; - No significant increase in SUA was observed in the 75 mg/kg and 100 mg/kg dose groups, with 200 mg/kg being the optimal modeling dose; Molecular indicators: - Liver: PNP mRNA expression was upregulated 2.36-fold (p<0.05), while XO mRNA and protein expression were significantly decreased (p<0.05); - Kidney: No significant changes were observed in the mRNA and protein expression of transporters such as URAT1, OAT4, and ABCG2; Specificity verification: Allopurinol, febuxostat, and urodixin significantly reversed inosine-induced SUA. The increase (p<0.01) confirms that the model can be used for screening anti-hyperuric acid drugs.

*Precautions： No animals died during the study, and all animals fully recovered by the end of the experiment.

*References：Tang DH,et,al. Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model. Pharm Biol. 2021 Dec;59(1):175-182.