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Expression and function of Oat1 and Oat3 in rat kidney exposed to mercuric chloride

  • Inorganic Compounds
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Abstract

This study was designed to evaluate the expression and function of the organic anion transporters, Oat1 and Oat3, in rats exposed to a nephrotoxic dose of HgCl2. Oat1 protein expression increased in renal homogenates and decreased in renal basolateral membranes from HgCl2 rats, while Oat3 protein abundance decreased in both kidney homogenates and basolateral membranes. The lower protein levels of Oat1 and Oat3 in basolateral membranes explain the lower uptake capacity for p-aminohippurate (in vitro assays) and the diminution of the systemic clearance of this organic anion (in vivo studies) observed in treated rats. Since both transporters mediate mercury access to the renal cells, their down-regulation in basolateral membranes might be a defensive mechanism developed by the cell to protect itself against mercury injury. The pharmacological modulation of the expression and/or the function of Oat1 and Oat3 might be an effective therapeutic strategy for reducing the nephrotoxicity of mercury.

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Acknowledgments

This study was supported by the following grants: FONCYT and CONICET. The authors thank to Prof. Héctor R. Girolami (Area Toxicología, Facultad de Ciencias Bioquímicas y Farmacéuticas, U.N.R.) for his important collaboration in this work and to Mrs Alejandra Martínez (Area Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, U.N.R.) for her technical assistance with the histological studies. The authors also thank Wiener Lab Argentina for analytical kits.

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Authors and Affiliations

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

    Gisela Di Giusto & Adriana M. Torres

  2. Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan

    Naohiko Anzai & Hitoshi Endou

  3. Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Suipacha 531, Rosario, (2000), Argentina

    María L. Ruiz

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  1. Gisela Di Giusto
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  2. Naohiko Anzai
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  3. María L. Ruiz
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  4. Hitoshi Endou
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  5. Adriana M. Torres
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Correspondence to Adriana M. Torres.

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Di Giusto, G., Anzai, N., Ruiz, M.L. et al. Expression and function of Oat1 and Oat3 in rat kidney exposed to mercuric chloride. Arch Toxicol 83, 887–897 (2009). https://doi.org/10.1007/s00204-009-0445-8

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  • DOI: https://doi.org/10.1007/s00204-009-0445-8

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