Establishment of a novel hyperuricemiaanimal model using mice and assessment ofhyporuricemia action of PNP inhibitor Ulodesine
10.3969/j.issn.1001-1978.2017.06.027
- VernacularTitle:以PNP酶为靶点的急性高尿酸血症小鼠模型组建
- Author:
Xujuan YANG
;
Xi HUANG
;
Zhou TIAN
;
Ping WANG
;
Penghui LI
;
Jianwen ZHANG
- Keywords:
purine nucleoside phosphorylase(PNP);
hyperuricemia;
Ulodesine;
inosine;
mice;
acute animal model
- From:
Chinese Pharmacological Bulletin
2017;33(6):883-886
- CountryChina
- Language:Chinese
-
Abstract:
Aim To establish a novel acute hyperuricemia mouse model and apply it to evaluate the hyporucicemia effects of Ulodesine, a purine nucleoside phosphorylase(PNP) inhibitor.Methods The mice were intraperitoneal injected inosine and subcutaneous injected Oteracil potassium to induce accumulation of uric acid, and the animal blood was collected from eyeball or vena angularis in different time points.The levels of serum uric acid were measured and determined to test whether the acute hyperuricemia mouse model were successful or not.In order to verify the hyperuricemia seen in the model was associated with the accumulation of inosine, which was converted to uric acid by action of PNP,hyporucicemia effects of Ulodesine, a PNP inhibitor, was assessed in an enzyme assay and confirmed by using the newly established model.Result Accumulation of uric acid in the blood of mouse models was observed by combined injections of intraperitoneal 200 mg·kg-1 inosine and subcutaneous 200 mg·kg-1 Oteracil potassium respectively after 1.5 h.The enzyme assay indicated that Ulodesine was a potently PNP inhibitor with IC50 of 2.293 nmol·L-1.IV injection of Ulodesine eliminated uric acid accumulations in blood of the mouse model, which was expected as the in vivo action of Ulodesine.Conclusions A novel acute hyperuricemia mouse model is established.This is a relatively easy and more effective protocol to generate the hyperuricemia in mice, which will be a useful platform to assess the anti-hyperuricemia activity of PNP-target drugs in vivo.
