Effects of oral exposure to arsenite on arsenic metabolism and transport in rat kidney

Abstract

Nephrotoxicity is within the recognized toxic effects of arsenic. In this study we assessed the effect of arsenite on the renal capacity to metabolize and handle arsenicals in rats exposed to drinking water with 0, 1, 5, or 10 ppm sodium arsenite for ten days. Arsenite treatment did not affect the gene expression of the main enzyme catalyzing methylation of arsenite, As3mt, while it reduced the expression of GSTO1 mRNA and protein. Arsenite decreased the expression of Aqp3, Mrp1, Mrp4, and Mdr1b (i.e., transporters and channels used by arsenic), but not that of Aqp7, Glut1, Mrp2, and Mdr1a. The protein abundance of AQP3 was also reduced by arsenite. Arsenite increased urinary NGAL and FABP3 and decreased Klotho plasma levels, without alteration of creatinine, which evidenced early tubular damage. Renal Klotho mRNA and protein expressions were also downregulated, which may exacerbate renal damage. No effect was observed in selected miRNAs putatively associated with renal injury. Plasma PTH and FGF23 were similar between groups, but arsenite decreased the renal expression of Fgfr1 mRNA. In conclusion, exposure to arsenite alters the gene expression of proteins involved in the cellular handling of arsenical species and elicits tubular damage.