7-Hydroxycoumarin and its conjugated metabolites interact with organic anion transporters 1 and 3 in vitro and in vivo.

adefovir conjugates drug interactions nephrotoxicity organic anion transporter pharmacokinetics

Journal

Chemico-biological interactions
ISSN: 1872-7786
Titre abrégé: Chem Biol Interact
Pays: Ireland
ID NLM: 0227276

Informations de publication

Date de publication:
29 Oct 2024
Historique:
received: 17 08 2024
revised: 15 10 2024
accepted: 28 10 2024
medline: 1 11 2024
pubmed: 1 11 2024
entrez: 31 10 2024
Statut: aheadofprint

Résumé

7-Hydroxycoumarin (7-HC) is a natural coumarin compound rich in Chinese herbal medicines and has various pharmacological activities. After oral administration of 7-HC in rodents, its conjugated metabolites 7-hydroxycoumarin-β-D-glucuronide (7-HCG) and 7-hydroxycoumarin sulfate (7-HCS), exhibit high systemic exposure and urinary excretion. Organic anion transporters 1 and 3 (OAT1 and OAT3), mainly expressed in the proximal renal tubules, play an important role in drug-drug interactions and drug-induced kidney injury. We aimed to explore the mechanisms of OAT-mediated drug interactions and renal protective mechanisms of 7-HC and its conjugates. OAT-overexpressing cell models revealed that 7-HC was not a substrate for OAT1 and OAT3, while 7-HCG was specifically transported by OAT3. In contrast, 7-HCS can be transported by both OATs. Besides, 7-HC significantly inhibited the activity of OAT1 and OAT3, while 7-HCS had a strong inhibitory effect on OAT1 (IC

Identifiants

DOI: 10.1016/j.cbi.2024.111293 PMID: 39481674
pubmed: 39481674
pii: S0009-2797(24)00439-3
doi: 10.1016/j.cbi.2024.111293
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

111293

Informations de copyright

Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Lijun Luo (L)

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: luolijun@imm.ac.cn.

Yongchun Chang (Y)

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: cyongchun@imm.ac.cn.

Weilin Zhang (W)

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: zhangweilin@imm.ac.cn.

Xiao Liu (X)

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: liuxiao_tr@163.com.

Junpu Ge (J)

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: gjpbbml@163.com.

Jieyi Chen (J)

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: chenjieyi@imm.ac.cn.

Yan Li (Y)

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: yanli@imm.ac.cn.

Dan Zhang (D)

Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: danzhang@imm.ac.cn.

Li Sheng (L)

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: shengli@imm.ac.cn.

Classifications MeSH