Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model

Abstract

Context

The uric acid metabolism pathway is more similar in primates and humans than in rodents. However, there are no reports of using primates to establish animal models of hyperuricaemia (HUA).

Objectives

To establish an animal model highly related to HUA in humans.

Materials and methods

Inosine (75, 100 and 200 mg/kg) was intraperitoneally administered to adult male rhesus monkeys (n = 5/group). Blood samples were collected over 8 h, and serum uric acid (SUA) level was determined using commercial assay kits. XO and PNP expression in the liver and URAT1, OAT4 and ABCG2 expression in the kidneys were examined by qPCR and Western blotting to assess the effects of inosine on purine and uric acid metabolism. The validity of the acute HUA model was assessed using ulodesine, allopurinol and febuxostat.

Results

Inosine (200 mg/kg) effectively increased the SUA level in rhesus monkeys from 51.77 ± 14.48 at 0 h to 178.32 ± 14.47 μmol/L within 30 min and to peak levels (201.41 ± 42.73 μmol/L) at 1 h. PNP mRNA level was increased, whereas XO mRNA and protein levels in the liver were decreased by the inosine group compared with those in the control group. No changes in mRNA and protein levels of the renal uric acid transporter were observed. Ulodesine, allopurinol and febuxostat eliminated the inosine-induced elevation in SUA in tested monkeys.

Conclusions

An acute HUA animal model with high reproducibility was induced; it can be applied to evaluate new anti-HUA drugs in vivo and explore the disease pathogenesis.

Keywords:

• Inosine
• uric acid
• hyperuricaemia
• animal model

Disclosure statement

The authors report that there are no conflicts of interest.

Additional information

Funding

This work was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) under Grant Numbers 2016-I2M-2-006 and 2019-I2M-1-004.