title: Effects of phosphate binders on the gastrointestinal absorption of arsenate and of an SGLT2 inhibitor drug on the urinary excretion of arsenite in mice.
abstract: Arsenate (AsV) and arsenite (AsIII) are typical sources of acute and chronic arsenic poisoning. Therefore, reducing inner exposure to these arsenicals is a rational objective. Because AsVmimics phosphate, phosphate binder drugs may decrease the intestinal AsVabsorption. Indeed, lanthanum and aluminium salts and sevelamer removed AsVfrom solution in vitro, especially at acidic pH. In mice gavaged with AsV, lanthanum chloride, lanthanum carbonate and aluminium hydroxide given orally also lowered the urinary excretion and tissue levels of AsVand its metabolites, indicating that they decreased the gastrointestinal AsVabsorption. As some glucose transporters may carry AsIII, the effect of the SGLT2 inhibitor dapagliflozin was investigated in AsIII-injected mice. While producing extreme glucosuria, dapagliflozin barely affected the urinary excretion and tissue concentrations of AsIIIand its metabolites. Thus, phosphate binders (especially lanthanum compounds) can reduce the gastrointestinal absorption of AsV; however, SGLT2 inhibition cannot diminish the renal reabsorption of AsIII.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7624, Pécs, Hungary; Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7624, Pécs, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Poór
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7624, Pécs, Hungary; Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7624, Pécs, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Németi
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7624, Pécs, Hungary. Electronic address: zoltan.gregus@aok.pte.hu.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Gregus
mesh_terms: D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000818:Animals; D001149:Arsenates / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018053:Arsenites / Q000652:urine; D001559:Benzhydryl Compounds / Q000494:pharmacology; D005260:Female; D065569:Gastrointestinal Absorption / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010710:Phosphates; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001149:Arsenates; D018053:Arsenites; D001559:Benzhydryl Compounds; D005960:Glucosides; D010710:Phosphates; C490299:Slc5a2 protein, mouse; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C028521:lanthanum chloride; C529054:dapagliflozin; C119467:lanthanum carbonate; D000536:Aluminum Hydroxide; D007811:Lanthanum; C015001:arsenite
keywords: Aluminium hydroxide; Arsenic; Dapagliflozin; Lanthanum carbonate; SGLT2; Sevelamer