Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model
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...
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doaj-88c17a79642e49f487cae198bdcbd6d22021-03-18T15:12:46ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162021-01-0159117518210.1080/13880209.2020.18713731871373Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal modelDong-hong Tang0Chen-yun Wang1Xi Huang2Hong-kun Yi3Zhe-li Li4Kai-li Ma5You-song Ye6Jian-wen Zhang7Medical Primate Research Center of China, Institute of Medical Biology, Chinese Academy of Medical Sciences/Peking Union Medical CollegeMedical Primate Research Center of China, Institute of Medical Biology, Chinese Academy of Medical Sciences/Peking Union Medical CollegeKPC Pharmaceuticals IncMedical Primate Research Center of China, Institute of Medical Biology, Chinese Academy of Medical Sciences/Peking Union Medical CollegeMedical Primate Research Center of China, Institute of Medical Biology, Chinese Academy of Medical Sciences/Peking Union Medical CollegeMedical Primate Research Center of China, Institute of Medical Biology, Chinese Academy of Medical Sciences/Peking Union Medical CollegeMedical Primate Research Center of China, Institute of Medical Biology, Chinese Academy of Medical Sciences/Peking Union Medical CollegeKPC Pharmaceuticals IncContext 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.http://dx.doi.org/10.1080/13880209.2020.1871373inosineuric acidhyperuricaemiaanimal model |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dong-hong Tang Chen-yun Wang Xi Huang Hong-kun Yi Zhe-li Li Kai-li Ma You-song Ye Jian-wen Zhang |
spellingShingle |
Dong-hong Tang Chen-yun Wang Xi Huang Hong-kun Yi Zhe-li Li Kai-li Ma You-song Ye Jian-wen Zhang Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model Pharmaceutical Biology inosine uric acid hyperuricaemia animal model |
author_facet |
Dong-hong Tang Chen-yun Wang Xi Huang Hong-kun Yi Zhe-li Li Kai-li Ma You-song Ye Jian-wen Zhang |
author_sort |
Dong-hong Tang |
title |
Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model |
title_short |
Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model |
title_full |
Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model |
title_fullStr |
Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model |
title_full_unstemmed |
Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model |
title_sort |
inosine induces acute hyperuricaemia in rhesus monkey (macaca mulatta) as a potential disease animal model |
publisher |
Taylor & Francis Group |
series |
Pharmaceutical Biology |
issn |
1388-0209 1744-5116 |
publishDate |
2021-01-01 |
description |
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. |
topic |
inosine uric acid hyperuricaemia animal model |
url |
http://dx.doi.org/10.1080/13880209.2020.1871373 |
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