RESUMEN
BACKGROUND: Uricase (Uox) is a major drug in gout and a supplementary drug in cancer treatment. Because allergic reactions caused by Uox limit its clinical application,10% Co/EDTA was used to chemically modify Uox from A. flavus to reduce its immunogenicity. METHODS: The immunogenicity of Uox and 10% Co/EDTA-Uox was examined by determining the antibody titer and concentration of IL-2, IL-6, IL-10, and TNF-ß in quail and rat serum. Moreover, we examined the pharmacokinetics of 10% Co/EDTA-Uox in rats and acute toxicity in mice. RESULTS: The concentration of UA decreased from 771.85 ±180.99 to 299.47 ±20.37 µmoL/Lï¼p<0.01ï¼ in the hyperuricemia model of quails injected by 10% Co/EDTA-Uox. Two-way immuno-diffusion electrophoresis revealed that 10% Co/EDTA-Uox did not produce antibody, whereas the antibody titer against Uox was 1:16. The concentrations of four cytokines in the 10% Co/EDTA-Uox group were significantly lower than in Uox group (p < 0.01)ï¼ The titer of IgG and IgM against 10% Co/EDTA-Uox was significantly lower than that against Uox at different serum dilutions (p < 0.0001). The pharmacokinetic data indicated that the half-life time of 10% Co/EDTA- Uox( 69.315h) was significantly longer than that of Uox(13.4 h)ï¼p<0.01ï¼. The tissue section of the liver, heart, kidney, and spleen revealed no toxicity in Uox and 10% Co/EDTA- Uox groups. CONCLUSION: 10% Co/EDTA-Uox possesses little immunogenicity, a long half-life time, and a highly efficient degradation of UA.