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 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.
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Ellappan
E
Babu
Michio
M
Takeda
Ritsuo
R
Nishida
Rie
R
Noshiro-Kofuji
Masaaki
M
Yoshida
Shiro
S
Ueda
Toshiyuki
T
Fukutomi
Naohiko
N
Anzai
Hitoshi
H
Endou
D000818:Animals; D000838:Anions / Q000378:metabolism*; D034341:Aristolochic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal; D027361:Organic Anion Transporters / Q000494:pharmacology*; D011339:Probenecid / Q000494:pharmacology
D000838:Anions; D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; D027361:Organic Anion Transporters; C000228:aristolochic acid I; D011339:Probenecid