Document Detail


Interactions of human organic anion transporter 1 (hOAT1) with substances associated with forensic toxicology.
MedLine Citation:
PMID:  21561794     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Renal excretion is an important elimination pathway for substances associated with forensic toxicology, such as medicines, agricultural chemicals, and industrial chemicals. This study aimed to elucidate the renal elimination pathway of substances using culture cells stably expressing the human organic anion transporter 1 (hOAT1) gene. Substances tested were diazepam, triazolam, haloperidol, amitriptyline, mianserin, bromovalerylurea, phenobarbital, acetaminophen, acetylsalicylic acid, lidocaine, aconitine, atropine, caffeine, nicotine, malathion, dichlorvos, fenitrothion, chlorpyrifosmethyl, paraquat, diquat, potassium cyanide, sodium arsenite, sodium azide, o-cresol, and probenecid (control, a representative inhibitor of hOAT1). Results demonstrated that diazepam, triazolam, amitriptyline, mianserin, malathion, fenitrothion, chlorpyrifosmethyl, and probenecid significantly inhibited representative substrates of hOAT1 and para-aminohippuric acid uptake by hOAT1. IC(50) values of the aforementioned substances were 133.3, 185.2, 354.1, 312.6, 114.2, 26.6, 191.5, and 7.9μM, respectively. Ki values were 83.5, 86.0, 573.9, 99.0, 134.0, 51.2, 324.6, and 9.1μM, respectively. In conclusion, the current results suggest that fenitrothion and chlorpyrifosmethyl are transported with pharmacokinetics indicative of hOAT1 involvement in the human kidney.
Authors:
Shoetsu Chiba; Toru Ikawa; Hiroshi Takeshita; Kazue Ichiba; Morihisa Sagi; Toshiji Mukai; Naohiro Anzai
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-9
Journal Detail:
Title:  Legal medicine (Tokyo, Japan)     Volume:  -     ISSN:  1873-4162     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100889186     Medline TA:  Leg Med (Tokyo)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan.
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