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Glomerular filtration drug injury: in vitro evaluation of functional and morphological podocyte perturbations

Research output: Contribution to journalArticle

  • Olivier Delézay
  • Zhiguo He
  • Sophie Hodin
  • Moin A Saleem
  • Patrick Mismetti
  • Nathalie Perek
  • Xavier Delavenne
Original languageEnglish
Pages (from-to)300-307
Number of pages8
JournalExperimental Cell Research
Volume361
Issue number2
Early online date26 Oct 2017
DOIs
DateAccepted/In press - 25 Oct 2017
DateE-pub ahead of print - 26 Oct 2017
DatePublished (current) - 15 Dec 2017

Abstract

The kidney is an organ that plays a major role in the excretion of numerous compounds such as drugs and chemicals. However, a great number of pharmacological molecules are nephrotoxic, affecting the efficiency of the treatment and increasing morbidity or mortality. Focusing on glomerular filtration, we propose in this study a simple and reproducible in vitro human model that is able to bring to light a functional podocyte injury, correlated with morphologic/phenotypic changes after drug exposure. This model was used for the evaluation of paracellular permeability of FITC-dextran molecules as well as FITC-BSA after different treatments. Puromycin aminonucleoside and adriamycin, compounds known to induce proteinuria in vivo and that serve here as positive nephrotoxic drug controls, were able to induce an important increase in fluorescent probe passage through the cell monolayer. Different molecules were then evaluated for their potential effect on podocyte filtration. Our results demonstrated that a drug effect could be time dependent, stable or scalable and relatively specific. Immunofluorescence studies indicated that these functional perturbations were due to cytoskeletal perturbations, monolayer disassembly or could be correlated with a decrease in nephrin expression and/or ZO-1 relocation. Taken together, our results demonstrated that this in vitro human model represents an interesting tool for the screening of the renal toxicity of drugs.

    Research areas

  • Drug podocyte injury, Albuminuria In vitro functional toxicity, Permeability

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier at https://doi.org/10.1016/j.yexcr.2017.10.031 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 1 MB, PDF document

    Licence: CC BY-NC-ND

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