title: Arsenic and Mercury Containing Traditional Chinese Medicine (Realgar and Cinnabar) Strongly Inhibit Organic Anion Transporters, Oat1 and Oat3, In Vivo in Mice.
abstract: Toxic heavy metals, including mercury (Hg) and arsenic (As), accumulate preferentially in kidneys and always cause acute renal failure. The aim of this study was to investigate whether these samples affect organic anion transporters, Oat1 and Oat3, in vivo in mice kidney. Mice (n = 10) were orally treated with investigational samples. After last administration, all mice were i.v. p-aminohippuric acid (PAH), and the blood and kidneys samples were collected. The concentrations of PAH were quantified by spectrophotometry. mRNA expressions of Oat1 and Oat3 were assayed by real-time PCR. In comparison with corresponding control, major pharmacokinetic parameters of PAH in sera were significantly changed by investigational samples (p < 0.05), PAH accumulations in the kidney tissues were significantly higher (p < 0.05), PAH uptake by renal slices was greatly reduced, Oat1 and Oat3 mRNA expression were significantly inhibited in investigational sample groups. Arsenic and mercury containing traditional Chinese medicine (Realgar and Cinnabar) probably induce kidney damage through inhibiting several members of the organic anion transporters (such as OAT1 and OAT3).
authors.affiliation: Department of Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Qi
authors.affiliation: Department of Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Sun
authors.affiliation: Pharmacy Department, Zhumadian People's Hospital, Zhumadian, Henan 463000, China.
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Pharmacy Department, Nanhai Hospital of Chinese Medicine, Foshan, Guangdong 528200, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Lin
mesh_terms: D000818:Animals; D001151:Arsenic / Q000008:administration & dosage / Q000009:adverse effects*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D008516:Medicine, Chinese Traditional / Q000009:adverse effects*; D008628:Mercury / Q000008:administration & dosage / Q000009:adverse effects*; D051379:Mice; D027362:Organic Anion Transport Protein 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C105033:Slc22a6 protein, mouse; C114338:organic anion transport protein 3; D008628:Mercury; D001151:Arsenic