Interactions of Human Organic Anion Transporters With Aristolochic Acids

Aristolochic acids (AAs), contained in Chinese herbal preparations, have been considered to induce nephropathy. In order to elucidate the molecular mechanisms of AA-induced nephrotoxicity, we have elucidated the interaction of human organic anion transporters (hOATs) with AAs using their stable cell...

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Main Authors: Ellappan Babu, Michio Takeda, Ritsuo Nishida, Rie Noshiro-Kofuji, Masaaki Yoshida, Shiro Ueda, Toshiyuki Fukutomi, Naohiko Anzai, Hitoshi Endou
Format: Article
Language:English
Published: Elsevier 2010-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319309454
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spelling doaj-e627bb26fe4b4bdb93271f1bbb2d9b4d2020-11-25T01:33:27ZengElsevierJournal of Pharmacological Sciences1347-86132010-01-011132192196Interactions of Human Organic Anion Transporters With Aristolochic AcidsEllappan Babu0Michio Takeda1Ritsuo Nishida2Rie Noshiro-Kofuji3Masaaki Yoshida4Shiro Ueda5Toshiyuki Fukutomi6Naohiko Anzai7Hitoshi Endou8Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanLaboratory of Chemical Ecology, Division of Applied Life Sciences, Faculty of Agriculture, Kyoto University, Kyoto 606-8502, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanKotarou Kanppo Co., Ltd., Osaka 531-0071, JapanDepartment of Pharmaceutical Information, Faculty of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, Japan; Corresponding author. anzai@ks.kyorin-u.ac.jpDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanAristolochic acids (AAs), contained in Chinese herbal preparations, have been considered to induce nephropathy. In order to elucidate the molecular mechanisms of AA-induced nephrotoxicity, we have elucidated the interaction of human organic anion transporters (hOATs) with AAs using their stable cell lines. AA-I and AA-II inhibited organic anion uptake by hOAT1, hOAT3, and hOAT4 in dose-dependent manners. Treatment of hOAT3 with AA-I resulted in a significant reduction in viability compared with that of mock, which was rescued by the organic anion transport inhibitor probenecid. In conclusion, hOAT3-mediated AA-I uptake may be associated with the induction of nephrotoxicity. Keywords:: aristolochic acid, organic anion transporter, aristolochic acid nephropathyhttp://www.sciencedirect.com/science/article/pii/S1347861319309454
collection DOAJ
language English
format Article
sources DOAJ
author Ellappan Babu
Michio Takeda
Ritsuo Nishida
Rie Noshiro-Kofuji
Masaaki Yoshida
Shiro Ueda
Toshiyuki Fukutomi
Naohiko Anzai
Hitoshi Endou
spellingShingle Ellappan Babu
Michio Takeda
Ritsuo Nishida
Rie Noshiro-Kofuji
Masaaki Yoshida
Shiro Ueda
Toshiyuki Fukutomi
Naohiko Anzai
Hitoshi Endou
Interactions of Human Organic Anion Transporters With Aristolochic Acids
Journal of Pharmacological Sciences
author_facet Ellappan Babu
Michio Takeda
Ritsuo Nishida
Rie Noshiro-Kofuji
Masaaki Yoshida
Shiro Ueda
Toshiyuki Fukutomi
Naohiko Anzai
Hitoshi Endou
author_sort Ellappan Babu
title Interactions of Human Organic Anion Transporters With Aristolochic Acids
title_short Interactions of Human Organic Anion Transporters With Aristolochic Acids
title_full Interactions of Human Organic Anion Transporters With Aristolochic Acids
title_fullStr Interactions of Human Organic Anion Transporters With Aristolochic Acids
title_full_unstemmed Interactions of Human Organic Anion Transporters With Aristolochic Acids
title_sort interactions of human organic anion transporters with aristolochic acids
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2010-01-01
description Aristolochic acids (AAs), contained in Chinese herbal preparations, have been considered to induce nephropathy. In order to elucidate the molecular mechanisms of AA-induced nephrotoxicity, we have elucidated the interaction of human organic anion transporters (hOATs) with AAs using their stable cell lines. AA-I and AA-II inhibited organic anion uptake by hOAT1, hOAT3, and hOAT4 in dose-dependent manners. Treatment of hOAT3 with AA-I resulted in a significant reduction in viability compared with that of mock, which was rescued by the organic anion transport inhibitor probenecid. In conclusion, hOAT3-mediated AA-I uptake may be associated with the induction of nephrotoxicity. Keywords:: aristolochic acid, organic anion transporter, aristolochic acid nephropathy
url http://www.sciencedirect.com/science/article/pii/S1347861319309454
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