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Chloroacetaldehyde- and acrolein-induced death of human proximal tubule cells

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Abstract

Ifosfamide (ifo) is a commonly used drug in chemotherapy. It is metabolized to acrolein (acro) and chloroacetaldehyde (CAA), which are thought to be responsible for renal side effects. We studied the effects of ifo and cyclophosphamide (cyclo) as well as their metabolites, acro and CAA, on cellular protein content, necrosis, apoptosis and cytosolic calcium concentration using a human proximal tubule cell line. The protein content decreased during acro or CAA administration (15 to 300 µmol/l), but not during ifo or cyclo exposure over a time period of up to 72 h. Mild apoptosis was induced only by high acro (150, 300 µmol/l) and low CAA concentrations (15, 75 µmol/l) and only in a narrow time window (24 h). Necrosis was increased after exposure to acro or CAA at all concentrations. CAA was more potent than acro. Ifo and cyclo did not induce necrosis or apoptosis. Glutathione abolished CAA-induced cell death. Cytosolic calcium concentrations increased after acro or CAA administration and showed an oscillating pattern. Cytosolic Ca2+ chelation did not prevent necrosis. We conclude that neither ifo nor cyclo induce cell damage, but that their metabolites acro and CAA induce cell death. This cell death occurs mainly by necrosis and not by apoptosis.

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Acknowledgements

A.B. was supported by DFG grant BE 3168/1–1.

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Authors and Affiliations

  1. Institute of Physiology, University of Würzburg, Röntgenring 9, 97070, Würzburg, Germany

    Gerald Schwerdt, Andreas Benesic, Ruth Freudinger & Michael Gekle

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

    Nader Gordjani, Brigitte Wollny & Antje Kirchhoff

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  1. Gerald Schwerdt
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  2. Nader Gordjani
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Correspondence to Gerald Schwerdt.

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M. Gekle and N. Gordjani contributed equally to this work

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Schwerdt, G., Gordjani, N., Benesic, A. et al. Chloroacetaldehyde- and acrolein-induced death of human proximal tubule cells. Pediatr Nephrol 21, 60–67 (2006). https://doi.org/10.1007/s00467-005-2006-6

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  • DOI: https://doi.org/10.1007/s00467-005-2006-6

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