Interactions of Human Organic Anion Transporters With Aristolochic Acids

Journal of Pharmacological Sciences

Ellappan Babu¹  Michio Takeda¹  Rie Noshiro-Kofuji¹  Naohiko Anzai¹  Masaaki Yoshida⁴  Hitoshi Endou¹  Ritsuo Nishida³  Shiro Ueda²  Toshiyuki Fukutomi¹ 

[1] Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan;Department of Pharmaceutical Information, Faculty of Pharmaceutical Sciences, Chiba University, Japan;Laboratory of Chemical Ecology, Division of Applied Life Sciences, Faculty of Agriculture, Kyoto University, Japan;Kotarou Kanppo Co., Ltd., Japan

关键词: aristolochic acid;    organic anion transporter;    aristolochic acid nephropathy;   

DOI  :  10.1254/jphs.09339SC

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(15)Cited-By(13)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.

【 授权许可】

Unknown