title: High accumulation of arsenic in the esophagus of mice after exposure to arsenite.
abstract: Arsenic-induced toxicity appears to be dependent on the tissue- or cell-specific accumulation of this metalloid. An early study showed that arsenic was retained in the esophagus as well as the liver, kidney cortex and skin of marmosets after intraperitoneal administration of (74)As-arsenite. However, there is little available information regarding the distribution of arsenic in the esophagus. Here, we compared the retention of arsenic in the esophagus, liver, lung, kidney and heart in mice intraperitoneally administered 1 or 5 mg/kg sodium arsenite (As(III)) daily for 3 or 7 days. The results showed that the arsenic concentration was highest in the esophagus. We compared the mRNA levels of aquaglyceroporin (AQP) 3, AQP7 and AQP9, which are responsible for arsenic influx, and those of multidrug-resistance protein (MRP) 1 and MRP2, which are responsible for arsenic efflux. The levels of AQP3 mRNA in the esophagus were much higher than those in liver, lung and heart, while the mRNA levels of MRP2 were very low in the esophagus. In addition, we found extremely low expression of Nrf2 in the esophagus at the basal and under the activated conditions, which might have resulted in low levels of glutamyl-cysteine ligase catalytic and modulatory subunits, and subsequently in the low levels of glutathione. Thus, the highest retention of arsenic was detected in the esophagus after intraperitoneal administration of As(III) to mice, and this appeared to result from multiple factors, including high expression of AQP3, low expression of MRP2, low capacity of glutathione synthesis and low activation of Nrf2.
authors.affiliation: Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, 770-8514, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Sumi
authors.affiliation: Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, 770-8514, Japan.
authors.forename: Miyu
authors.initials: M
authors.lastname: Tsurumoto
authors.affiliation: Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, 770-8514, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yoshino
authors.affiliation: Laboratory of Functional Morphology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, 770-8514, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Showa-cho, Maebashi-city, Gunma, 371-8511, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Showa-cho, Maebashi-city, Gunma, 371-8511, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
authors.affiliation: Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, 770-8514, Japan. himenos@ph.bunri-u.ac.jp.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Himeno
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000818:Animals; D051400:Aquaporin 3 / Q000235:genetics*; D018053:Arsenites / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017670:Sodium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D013997:Time Factors; D014018:Tissue Distribution; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D051400:Aquaporin 3; D018053:Arsenites; D005978:Glutathione; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D017670:Sodium Compounds; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C496028:Aqp3 protein, mouse; C495636:Nfe2l2 protein, mouse; C017947:sodium arsenite
keywords: Aquaglyceroporin; Arsenic; Esophagus; Glutathione; Multidrug-resistance protein; Nrf2