Characterization and Immunogenicity of Recombinant A. flavus Uox Modified by Co/EDTA Carbon Dots


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Abstract

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.

About the authors

Hai-Ling Li

West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University

Email: info@benthamscience.net

Xiu-Feng Gao

West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University

Author for correspondence.
Email: info@benthamscience.net

Jing-Ji Li

College of Ecology and Environment,, Chengdu University of Technology

Email: info@benthamscience.net

Ming-Xia Wan

West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University

Email: info@benthamscience.net

Guo-Qi Zhang

Department of Chemistry, School of Science, Xihua University

Email: info@benthamscience.net

Yong-Sheng Li

School of Chemical Engineering, Sichuan University

Author for correspondence.
Email: info@benthamscience.net

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