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.
journal_name
Pharm Bioljournal_title
Pharmaceutical biologyauthors
Tang DH,Wang CY,Huang X,Yi HK,Li ZL,Ma KL,Ye YS,Zhang JWdoi
10.1080/13880209.2020.1871373keywords:
["Inosine","animal model","hyperuricaemia","uric acid"]subject
Has Abstractpub_date
2021-12-01 00:00:00pages
175-182issue
1eissn
1388-0209issn
1744-5116journal_volume
59pub_type
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