Effects of nonsteroidal anti-inflammatory drugs on the renal excretion of indoxyl sulfate, a nephro-cardiovascular toxin, in rats

Chung Ping Yu, Douglas H. Sweet, Yu Hsuan Peng, Yow Wen Hsieh, Pei Dawn Lee Chao, Yu Chi Hou, Shiuan Pey Lin*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

19 引文 斯高帕斯(Scopus)

摘要

Chronic kidney disease (CKD) is a health problem worldwide. Indoxyl sulfate (IS) is a nephro-cardiovascular toxin accumulated in CKD patients and cannot be removed through hemodialysis. The renal excretion of IS was mediated by organic anion transporters (OATs) OAT 1 and OAT 3. Because a number of nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to inhibit OATs, we hypothesize that NSAIDs might inhibit the renal excretion of IS. Rats were intravenously injected IS with and without diclofenac, ketoprofen or salicylic acid, individually. Blood samples were collected at predetermined time points and the concentrations of IS were determined by HPLC method. The results showed that diclofenac and ketoprofen at 10.0 mg/kg significantly decreased the systemic clearance of IS by 71% and 82%, and increased the MRT of IS by 106% and 105%, respectively, whereas salicylic acid did not exhibit significant effects. Cell studies indicated that diclofenac and ketoprofen inhibited the uptake of IS mediated by OAT 1 and OAT 3. In conclusion, diclofenac and ketoprofen inhibited the excretion of IS through inhibition on OAT 1 and OAT 3.

原文英語
頁(從 - 到)66-70
頁數5
期刊European Journal of Pharmaceutical Sciences
101
DOIs
出版狀態已出版 - 01 04 2017
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© 2017 Elsevier B.V.

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