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Published on: November 5, 2013
Characterization and Immunogenicity of Recombinant A. flavus Uox Modified by Co/EDTA Carbon Dots
Hai-Ling Li1,2, Xiu-Feng Gao1, Jing-Ji Li2
1West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, P.R. China.
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-β 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/L (p<0.01) 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); 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 (69.315 h) was significantly longer than that of Uox (13.4 h) (p<0.01). 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.
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