title: 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 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.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan. chiba@marianna-u.ac.jp
authors.forename: Shoetsu
authors.initials: S
authors.lastname: Chiba
authors.forename: Toru
authors.initials: T
authors.lastname: Ikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshita
authors.forename: Kazue
authors.initials: K
authors.lastname: Ichiba
authors.forename: Morihisa
authors.initials: M
authors.lastname: Sagi
authors.forename: Toshiji
authors.initials: T
authors.lastname: Mukai
authors.forename: Naohiro
authors.initials: N
authors.lastname: Anzai
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000493:pharmacokinetics*; D053593:Forensic Toxicology; D006801:Humans; D007306:Insecticides / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D027361:Organic Anion Transporters / Q000378:metabolism*; D014162:Transfection
chemical_list: D002491:Central Nervous System Agents; D007306:Insecticides; D027361:Organic Anion Transporters; C530205:SLC22A13 protein, human