Potassium oxonate induces acute hyperuricemia in the tree shrew (tupaia belangeri chinensis)

Potassium oxonate, a selectively competitive uricase inhibitor, produced hyperuricemia (HUA) in rodents in a previous study. In this study, we employed the tree shrew as an animal model to study potassium oxonate-induced HUA. The effect of allopurinol (ALLO), a uric acid reducer, was also examined in this model. Potassium oxonate at doses of 5, 20, 40, 60, 80, 100, and 1,000 mg/kg was given intraperitoneally to tree shrews. The results showed that potassium oxonate can effectively increase the levels of uric acid in tree shrews at doses ranging from 40 to 100 mg/kg. Semiquantitative RT-PCR showed that the xanthine dehydrogenase/oxidase (XDH/XO) mRNA expression level was significantly higher in the liver tissue of tree shrews with high levels of uric acid. There were no changes in serum urea nitrogen, or serum creatinine values. ALLO can significantly decrease serum uric acid levels (P<0.01) and raise XDH/XO mRNA expression levels in the liver tissue of tree shrews with HUA. XDH/XO mRNA expression levels did not change in untreated tree shrews. Studies on acute toxicity in the tree shrew did not show any significantly abnormal signs. There were no adverse effects at the macroscopic level up to doses ≤100 mg/kg. Potassium oxonate induced acute HUA in tree shrews at lower doses compared with other animal models. Potassium oxonate-treated tree shrews may be a potential animal model for studying pathogenic mechanism and evaluating a new therapeutic agent for treatment of HUA in humans.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:66

Enthalten in:

Experimental animals - 66(2017), 3 vom: 05. Aug., Seite 209-216

Sprache:

Englisch

Beteiligte Personen:

Tang, Dong-Hong [VerfasserIn]
Ye, You-Song [VerfasserIn]
Wang, Chen-Yun [VerfasserIn]
Li, Zhe-Li [VerfasserIn]
Zheng, Hong [VerfasserIn]
Ma, Kai-Li [VerfasserIn]

Links:

Volltext

Themen:

268B43MJ25
4R7FFA00RX
5VT6420TIG
63CZ7GJN5I
Allopurinol
EC 1.17.1.4
EC 1.7.3.3
Enzyme Inhibitors
Hyperuricemia
Journal Article
Oxonic Acid
Potassium oxonate
RNA, Messenger
Tree shrew
Urate Oxidase
Uric Acid
Xanthine Dehydrogenase
Xanthine dehydrogenase/oxidase (XDH/XO)

Anmerkungen:

Date Completed 28.09.2017

Date Revised 13.11.2018

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1538/expanim.16-0096

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM269928812