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Time course of organic anion transporter 5 (Oat5) urinary excretion in rats treated with cisplatin: a novel urinary biomarker for early detection of drug-induced nephrotoxicity

  • Organ Toxicity and Mechanisms
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Abstract

Cisplatin is a widely used citostatic drug employed in the treatment of many solid tumors. Its principal side-effect is nephrotoxicity. The organic anion transporter 5 (Oat5) is exclusively expressed in the kidneys. The aim of this study was to evaluate the time course of Oat5 urinary excretion and changes in conventional biomarkers, such as creatinine and urea plasma levels (Urp and Crp), and protein and glucose urinary levels (Pu and Gluu), between others, and compared them to the onset and progression of histological changes after cisplatin treatment. Male Wistar rats were treated with cisplatin with 5 mg/kg b.w., i.p., and experiments were carried out after 2, 4, 7 and 14 days of treatment. Two days after cisplatin administration, only Oat5 urinary excretion was found markedly modified. On day 4, Urp, Crp, PU and GluU were increased. By the seventh day, a severe impairment in tubular architecture was observed, and from this point and thereon, Oat5 urinary excretion and PU showed a tendency to return to their basal values. Meanwhile, Urp, Crp and GluU tended to return to their basal values by the day 14 of treatment, when kidney morphology showed an important recovery. So Oat5 urinary abundance was elevated 2 days after cisplatin treatment, when no modifications of traditional markers of renal injury were still observed. Therefore, the results showed in this work, in addition to previous data obtained by our group, propose that Oat5 urinary excretion might potentially serve as a noninvasive early biomarker of cisplatin-induced nephrotoxicity.

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Acknowledgments

This study was supported by the following grants: Fondo para la Investigación Científica y Tecnológica (FONCYT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario (UNR). The authors thank to Prof. H. Endou and to Prof. N. Anzai (Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan) for kindly providing Oat5-specific antibodies and Mrs Alejandra Martínez (Area Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, U.N.R.) for her collaboration in the present work. The authors also thank Wiener Lab Argentina for analytical kits.

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

    Romina Paula Bulacio & Adriana Mónica Torres

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  1. Romina Paula Bulacio
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  2. Adriana Mónica Torres
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Correspondence to Adriana Mónica Torres.

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Bulacio, R.P., Torres, A.M. Time course of organic anion transporter 5 (Oat5) urinary excretion in rats treated with cisplatin: a novel urinary biomarker for early detection of drug-induced nephrotoxicity. Arch Toxicol 89, 1359–1369 (2015). https://doi.org/10.1007/s00204-014-1345-0

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