Interactions of human organic anion transporter 1 (hOAT1) with substances associated with forensic toxicology

Abstract 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 hu...

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Bibliographic Details
Published in:Legal medicine (Tokyo, Japan) Japan), 2011-07, Vol.13 (4), p.180-185
Main Authors: Chiba, Shoetsu, Ikawa, Toru, Takeshita, Hiroshi, Ichiba, Kazue, Sagi, Morihisa, Mukai, Toshiji, Anzai, Naohiro
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Central Nervous System Agents - pharmacokinetics
Forensic Toxicology
hOAT1
Humans
Insecticides - pharmacokinetics
Internal Medicine
Kidney - metabolism
Mice
Organic Anion Transporters - metabolism
para-Aminohippuric acid
Renal excretion
Substances associated with forensic toxicology
Transfection
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Summary:Abstract 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. IC50 values of the aforementioned substances were 133.3, 185.2, 354.1, 312.6, 114.2, 26.6, 191.5, and 7.9 μM, respectively. Ki values were 83.5, 86.0, 573.9, 99.0, 134.0, 51.2, 324.6, and 9.1 μM, respectively. In conclusion, the current results suggest that fenitrothion and chlorpyrifosmethyl are transported with pharmacokinetics indicative of hOAT1 involvement in the human kidney.
ISSN:1344-6223
1873-4162
DOI:10.1016/j.legalmed.2011.04.001