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Mesna or cysteine prevents chloroacetaldehyde-induced cell death of human proximal tubule cells

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Abstract

Chloroacetaldehyde (CAA) is formed in the body from the chemotherapeutically used drug ifosfamide (IFO). CAA leads to cell death in proximal tubule cells mainly through the mechanism of necrosis rather than apoptosis. During chemotherapy, 2-mercaptosulfonic acid (mesna) is used with IFO to protect the urothel from cell damage. Little is known of the effect of mesna on renal proximal tubule cells, the primary site of damage after IFO treatment. Mesna contains a sulfhydryl (SH) group. To clarify whether SH-group-containing molecules can prevent CAA-induced cell death, we studied the effect of mesna and cysteine on necrosis, apoptosis, and protein content in a human proximal tubule-derived cell line (IHKE cells) treated with CAA. Both substances prevented CAA-induced necrotic cell death and protein loss and restored CAA-inhibited caspase-3 activity. CAA also prevented cisplatin-induced apoptosis. This inhibition was reversible in the presence of glutathione (GSH). We conclude that SH-containing molecules can protect proximal tubule cells from cell death because they interact with CAA before CAA can disturb other important cellular SH groups. A sufficient supply of intra- and extracellular SH groups during IFO chemotherapy may therefore have the ability to protect renal tubule cells from cell death.

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Acknowledgements

AB was supported by DFG grant BE 3168/1-1

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Authors and Affiliations

  1. Department of Physiology, University of Würzburg, Würzburg, Germany

    Gerald Schwerdt, Ruth Freudinger, Andreas Benesic & Michael Gekle

  2. Children’s Hospital, University of Würzburg, Würzburg, Germany

    Antje Kirchhoff & Brigitte Wollny

  3. Physiologisches Institut, Universität Würzburg, Röntgenring 9, 97070, Würzburg, Germany

    Gerald Schwerdt

Authors
  1. Gerald Schwerdt
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  2. Antje Kirchhoff
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  3. Ruth Freudinger
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  4. Brigitte Wollny
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  5. Andreas Benesic
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  6. Michael Gekle
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Correspondence to Gerald Schwerdt.

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Schwerdt, G., Kirchhoff, A., Freudinger, R. et al. Mesna or cysteine prevents chloroacetaldehyde-induced cell death of human proximal tubule cells. Pediatr Nephrol 22, 798–803 (2007). https://doi.org/10.1007/s00467-006-0414-x

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  • DOI: https://doi.org/10.1007/s00467-006-0414-x

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