Critical Role of Organic Anion Transporters 1 and 3 in Kidney Accumulation and Toxicity of Aristolochic Acid I

2011 ◽  
Vol 8 (6) ◽  
pp. 2183-2192 ◽  
Author(s):  
Xiang Xue ◽  
Li-Kun Gong ◽  
Kazuya Maeda ◽  
Yang Luan ◽  
Xin-Ming Qi ◽  
...  
Keyword(s):  
Aristolochic Acid ◽  
Organic Anion ◽  
Critical Role ◽  
Organic Anion Transporters ◽  
Anion Transporters ◽  
Aristolochic Acid I

Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy

2020 ◽  
Vol 175 (2) ◽  
pp. 279-291
Author(s):  
Caiyu Li ◽  
Xue Wang ◽  
Yajuan Bi ◽  
Heshui Yu ◽  
Jing Wei ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Natural Compound ◽  
Aristolochic Acid ◽  
Organic Anion ◽  
Critical Role ◽  
Natural Compounds ◽  
Organic Anion Transporters ◽  
Herbal Products ◽  
Anion Transporters

Abstract Organic anion transporters 1 and 3 (OAT1 and OAT3) play a critical role in renal drug-drug interactions and are involved in the nephrotoxicity of many anionic xenobiotics. To date, relatively little is known about the interaction of natural compounds with OAT1 and OAT3. Of the 270 natural compounds screened in the present study, 21 compounds inhibited OAT1 and 45 compounds inhibited OAT3. Further concentration-dependent studies identified 7 OAT1 inhibitors and 10 OAT3 inhibitors with IC50 values of <10 μM, and most of them were flavonoids, the most commonly ingested polyphenolic compounds in the diet and herbal products. Computational modeling of OAT1 and OAT3 revealed the important residues for the recognition of inhibitors. The two strong OAT inhibitors, namely wedelolactone and wogonin, were evaluated for their in vivo interactions with the OAT substrate aristolochic acid I (AAI), a natural compound causing aristolochic acid-induced nephropathy (AAN) in many species. The cytotoxicity of AAI increased in two OAT-overexpressing cell lines, with more cytotoxicity in OAT1-overexpressing cells, suggesting a more important role of OAT1 than OAT3 in AAN. Both wedelolactone and wogonin markedly increased serum AAI concentrations in AAI-treated rats and ameliorated kidney injuries in AAI-treated mice. To conclude, the present findings are of significant value in understanding natural compound-drug interactions and provide a natural source for developing treatments for AAN.

Major role of organic anion transporters in the uptake of phenolsulfonphthalein in the kidney

2003 ◽  
Vol 475 (1-3) ◽  
pp. 85-92 ◽  
Author(s):  
Shirou Itagaki ◽  
Mitsuru Sugawara ◽  
Michiya Kobayashi ◽  
Sachiho Nishimura ◽  
Michio Fujimoto ◽  
...  
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporters ◽  
Anion Transporters

Role of Organic Anion Transporters in the Pharmacokinetics of Zonampanel, an α-Amino-3-hydroxy-5-methylisoxazole-4-propionate Receptor Antagonist, in Rats

2008 ◽  
Vol 36 (8) ◽  
pp. 1496-1504 ◽  
Author(s):  
Tsuyoshi Minematsu ◽  
Tadashi Hashimoto ◽  
Toshiko Aoki ◽  
Takashi Usui ◽  
Hidetaka Kamimura
Keyword(s):  
Receptor Antagonist ◽  
Organic Anion ◽  
Organic Anion Transporters ◽  
Anion Transporters

Molecular evidence for an involvement of organic anion transporters (OATs) in aristolochic acid nephropathy

Toxicology ◽  
2009 ◽  
Vol 264 (1-2) ◽  
pp. 74-79 ◽  
Author(s):  
Nadiya Bakhiya ◽  
Volker M. Arlt ◽  
Andrew Bahn ◽  
Gerhard Burckhardt ◽  
David H. Phillips ◽  
...  
Keyword(s):  
Aristolochic Acid ◽  
Organic Anion ◽  
Molecular Evidence ◽  
Organic Anion Transporters ◽  
Anion Transporters ◽  
Aristolochic Acid Nephropathy

scholarly journals Role of kidney-specific organic anion transporters in the urinary excretion of methotrexate

2001 ◽  
Vol 60 (3) ◽  
pp. 1058-1068 ◽  
Author(s):  
Ayako Takeuchi ◽  
Satohiro Masuda ◽  
Hideyuki Saito ◽  
Toshio Doi ◽  
Ken-Ichi Inui
Keyword(s):  
Urinary Excretion ◽  
Organic Anion ◽  
Organic Anion Transporters ◽  
Anion Transporters

scholarly journals ROLE OF RENAL ORGANIC ANION TRANSPORTERS, OAT-K1 AND OAT-K2, IN THE URINARY EXCRETION OF ANIONIC DRUGS

2000 ◽  
Vol 15 (supplement) ◽  
pp. 96-97
Author(s):  
Ayako Takeuchi ◽  
Satohiro Masuda ◽  
Hideyuki Saito ◽  
Ken-ichi Inui
Keyword(s):  
Urinary Excretion ◽  
Organic Anion ◽  
Organic Anion Transporters ◽  
Anion Transporters ◽  
Anionic Drugs

Adefovir accumulation and nephrotoxicity in renal interstitium: Role of organic anion transporters of kidney

Life Sciences ◽  
2019 ◽  
Vol 224 ◽  
pp. 41-50
Author(s):  
Yan Zhou ◽  
Yuquan Yang ◽  
Pei Wang ◽  
Mengmeng Wei ◽  
Yanrong Ma ◽  
...  
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporters ◽  
Renal Interstitium ◽  
Anion Transporters
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