Potassium Oxonate Induces Acute Hyperuricemia in the Tree Shrew (Tupaia Belangeri Chinensis)

Exp Anim. 2017 Aug 5;66(3):209-216. doi: 10.1538/expanim.16-0096. Epub 2017 Mar 16.

Abstract

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.

Keywords: allopurinol; hyperuricemia; potassium oxonate; tree shrew; xanthine dehydrogenase/oxidase (XDH/XO).

MeSH terms

  • Acute Disease
  • Allopurinol / pharmacology
  • Allopurinol / therapeutic use
  • Animals
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects*
  • Gene Expression
  • Humans
  • Hyperuricemia / chemically induced*
  • Hyperuricemia / drug therapy
  • Injections, Intraperitoneal
  • Liver / metabolism
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects*
  • RNA, Messenger / metabolism
  • Tupaia*
  • Urate Oxidase / antagonists & inhibitors
  • Uric Acid / metabolism
  • Xanthine Dehydrogenase / genetics
  • Xanthine Dehydrogenase / metabolism

Substances

  • Enzyme Inhibitors
  • RNA, Messenger
  • Uric Acid
  • potassium oxonate
  • Oxonic Acid
  • Allopurinol
  • Xanthine Dehydrogenase
  • Urate Oxidase