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Organic anion transporter 5 renal expression and urinary excretion in rats exposed to mercuric chloride: a potential biomarker of mercury-induced nephropathy

Archives of Toxicology volume 84, pages 741–749 (2010)Cite this article

Abstract

Mercuric chloride (HgCl2) induces acute kidney injury (AKI) affecting glomerular hemodynamics and, more specifically, the pars recta (S3 segment) of the proximal tubule. The organic anion transporter 5 (Oat5) is exclusively localized in the apical membranes of S3 segment. Oat5 urinary excretion was recently proposed as potential early biomarker of ischemic AKI. The aim of this study was to evaluate the renal expression and the urinary excretion of the Oat5 in rats exposed to HgCl2. Male Wistar rats were treated with a single injection of HgCl2 at different doses of 0, 0.2, 1 and 5 mg/kg body wt (control, Hg0.2, Hg1 and Hg5 groups). The renal expression of Oat5 was evaluated by immunohistochemistry, Western blotting, and real-time PCR. Oat5 and sodium dicarboxylate cotransporter 1 (NaDC1) abundances and alkaline phosphatase activity (AP) were assayed in urine. An HgCl2 dose-related decrease in Oat5 mRNA levels and in Oat5 protein levels in renal homogenates was observed. Hg5 rats showed an increase in urinary excretion of Oat5 and NaDC1 as well as alterations of other widely used parameters for renal dysfunction and injury (plasma creatinine, plasma urea, urinary AP activity, kidney weight, histological lesions). In Hg0.2 group only an increase of urinary excretion of Oat5 was observed. The increase of Oat5 urinary excretion in Hg1 group was associated to the beginning of tissular injury. These results suggest that urinary excretion of Oat5 might be an early indicator of mercury-induced nephropathy, which predicts the perturbation before the manifestation of histopathological damages.

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Acknowledgments

The present work was supported by the following grants: Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) de la República Argentina, PICT-2004 Nro: 020201 and PICT-2007 Nro: 00966; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) de la República Argentina, PIP Nro 5592 y PIP Nro. 01665. The authors thank Prof. H. Endou and Dr N. Anzai (Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan) for kindly providing Oat5 and NaDC1 specific antibodies; Prof. Héctor R. Girolami (Area Toxicología, Facultad de Ciencias Bioquímicas y Farmacéuticas, U.N.R.) for mercuric assays; Tec. Alejandra Martínez (Facultad de Ciencias Bioquímicas y Farmacéuticas, U.N.R.) for her contribution to the histological studies; Wiener Lab (Rosario, Argentina) for analytical kits.

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  1. Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Suipacha 531, 2000, Rosario, Argentina

    Gisela Di Giusto & Adriana Mónica Torres

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  1. Gisela Di Giusto
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  2. Adriana Mónica Torres
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Correspondence to Adriana Mónica Torres.

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Di Giusto, G., Torres, A.M. Organic anion transporter 5 renal expression and urinary excretion in rats exposed to mercuric chloride: a potential biomarker of mercury-induced nephropathy. Arch Toxicol 84, 741–749 (2010). https://doi.org/10.1007/s00204-010-0541-9

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Keywords

  • AKI
  • Mercuric nephrotoxicity
  • Oat5
  • NaDC1
  • Urinary biomarkers