Effects of phosphate binders on the gastrointestinal absorption of arsenate and of an SGLT2 inhibitor drug on the urinary excretion of arsenite in mice

摘要

Arsenate (As~Ⅴ) and arsenite (As~Ⅲ) are typical sources of acute and chronic arsenic poisoning. Therefore, reducing inner exposure to these arsenicals is a rational objective. Because As~Ⅴ mimics phosphate, phosphate binder drugs may decrease the intestinal As~Ⅴ absorption. Indeed, lanthanum and aluminium salts and sevelamer removed As~Ⅴ from solution in vitro, especially at acidic pH. In mice gavaged with As~Ⅴ, lanthanum chloride, lanthanum carbonate and aluminium hydroxide given orally also lowered the urinary excretion and tissue levels of As~Ⅴ and its metabolites, indicating that they decreased the gastrointestinal As~Ⅴ absorption. As some glucose transporters may carry As~Ⅲ, the effect of the SGLT2 inhibitor dapagliflozin was investigated in As~Ⅲ-injected mice. While producing extreme glucosuria, dapagliflozin barely affected the urinary excretion and tissue concentrations of As~Ⅲ and its metabolites. Thus, phosphate binders (especially lanthanum compounds) can reduce the gastrointestinal absorption of As~Ⅴ;however, SGLT2 inhibition cannot diminish the renal reabsorption of As~Ⅲ.