化学
免疫原性
色谱法
生物化学
抗体
免疫学
生物
作者
Xiu-Feng Gao,Yongsheng Li,Hailing Li,Jingji Li,Ming-Xia Wan,Guo-Qi Zhang
出处
期刊:Current Pharmaceutical Biotechnology
[Bentham Science]
日期:2024-02-01
卷期号:25 (2): 230-246
标识
DOI:10.2174/1389201024666230519144615
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI