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

doi:10.1016/j.ejps.2017.02.007

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	66-70
Number of pages	5
Journal	European Journal of Pharmaceutical Sciences
Volume	101
DOIs	https://doi.org/10.1016/j.ejps.2017.02.007
State	Published - 01 04 2017
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

Chronic kidney disease
Indoxyl sulfate
NSAIDs
Organic anion transporters
Uremic toxin

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10.1016/j.ejps.2017.02.007

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

abstract = "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.",

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author = "Yu, {Chung Ping} and Sweet, {Douglas H.} and Peng, {Yu Hsuan} and Hsieh, {Yow Wen} and Chao, {Pei Dawn Lee} and Hou, {Yu Chi} and Lin, {Shiuan Pey}",

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doi = "10.1016/j.ejps.2017.02.007",

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AU - Yu, Chung Ping

AU - Sweet, Douglas H.

AU - Peng, Yu Hsuan

AU - Hsieh, Yow Wen

AU - Chao, Pei Dawn Lee

AU - Hou, Yu Chi

AU - Lin, Shiuan Pey

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

KW - Chronic kidney disease

KW - Indoxyl sulfate

KW - NSAIDs

KW - Organic anion transporters

KW - Uremic toxin

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ER -

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

Abstract

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Keywords

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