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评估氧化铈作为一种磷酸盐结合剂在 5/6 肾切除模型大鼠中的应用。

Evaluation of cerium oxide as a phosphate binder using 5/6 nephrectomy model rat.

机构信息

applause Company Limited, Biko building 4F, Shinkawa 2-24-2, Chuo-ku, Tokyo, 104-0033, Japan.

Molecular Cell Biology Laboratory, Department of Systems Engineering and Science, Graduate School of Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama, 337-8570, Japan.

出版信息

BMC Nephrol. 2022 Aug 8;23(1):277. doi: 10.1186/s12882-022-02904-6.

DOI:10.1186/s12882-022-02904-6
PMID:35941569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9358871/
Abstract

BACKGROUND

The number of chronic kidney disease (CKD) patients continues to increase worldwide. CKD patients need to take phosphate binders to manage serum phosphorus concentrations. Currently, several types of phosphate binder, including lanthanum carbonate, are used. However, they each have disadvantages.

METHODS

In this study, we evaluated cerium oxide as a new phosphate binder in vitro and in vivo. First, cerium oxide was mixed with phosphoric acid at pH 2.5 or 7.0, and residual phosphoric acid was measured by absorption photometry using colorimetric reagent. Second, cerium oxide was fed to 5/6 nephrectomy model rats (5/6Nx), a well-known renal damage model. All rats were measured food intake, water intake, feces volume, and urine volume, and collected serum and urine were analyzed for biochemical markers.

RESULTS

Cerium oxide can adsorb phosphate at acidic and neutral pH, while lanthanum carbonate, which is a one of popular phosphate binder, does not dissolve at neutral pH. Cerium oxide-treatment reduced serum phosphate concentrations of 5/6Nx rats without an increase in serum alanine transaminase levels that would indicate hepatotoxicity, and cerium oxide-treatment maintained serum creatinine and blood urea nitrogen levels, while those of normal 5/6Nx rats increased slightly.

CONCLUSIONS

These results suggest that cerium oxide can be a potential phosphate binder. Decreased body weight gain and increased water intake and urine volume in 5/6Nx rats were thought to be an effect of nephrectomy because these changes did not occur in sham operation rats. Additional investigations are needed to evaluate the longer-term safety and possible accumulation of cerium oxide in the body.

摘要

背景

全球慢性肾脏病(CKD)患者人数持续增加。CKD 患者需要服用磷酸盐结合剂来控制血清磷浓度。目前,有几种类型的磷酸盐结合剂,包括碳酸镧等,但都有各自的缺点。

方法

本研究评估了氧化铈作为一种新型磷酸盐结合剂在体外和体内的效果。首先,将氧化铈与 pH 值为 2.5 或 7.0 的磷酸混合,并用比色法测定残留的磷酸。其次,将氧化铈喂给 5/6 肾切除模型大鼠(5/6Nx),这是一种著名的肾损伤模型。所有大鼠均测量了食物摄入量、饮水量、粪便量和尿量,并收集血清和尿液进行生化标志物分析。

结果

氧化铈可在酸性和中性 pH 下吸附磷酸盐,而作为一种常用的磷酸盐结合剂的碳酸镧在中性 pH 下不溶解。氧化铈治疗可降低 5/6Nx 大鼠的血清磷酸盐浓度,而不会导致血清丙氨酸氨基转移酶水平升高,这表明没有肝毒性,且氧化铈治疗可维持血清肌酐和血尿素氮水平,而正常 5/6Nx 大鼠的这些水平略有升高。

结论

这些结果表明,氧化铈可能是一种潜在的磷酸盐结合剂。5/6Nx 大鼠体重增加减少、饮水量和尿量增加被认为是肾切除的影响,因为这些变化在假手术大鼠中并未发生。需要进一步研究来评估氧化铈的长期安全性和体内可能的蓄积。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0a/9358871/8e228d54ebfe/12882_2022_2904_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0a/9358871/8657834999f0/12882_2022_2904_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0a/9358871/7860a8f7b6f9/12882_2022_2904_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0a/9358871/925ddd1e868c/12882_2022_2904_Fig8_HTML.jpg
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