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In vivo mesna and amifostine do not prevent chloroacetaldehyde nephrotoxicity in vitro

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Abstract

Chloroacetaldehyde (CAA) is the putative metabolite responsible for ifosfamide-induced nephrotoxicity. Whereas evidence suggests that sodium 2-mercaptoethanesulfonate (mesna) and amifostine protect renal cells against CAA toxicity in vitro, their efficacy in clinical studies is controversial. To better understand the discrepancy between in vivo and in vitro results, we combined the in vivo intraperitoneal administration of either saline or mesna (100 mg/kg) or amifostine (200 mg/kg) in rats and the in vitro study of CAA toxicity to both proximal tubules and precision-cut renal cortical slices. The measured renal cortical concentrations of mesna and amifostine were 0.6±0.1 μmol/g and 1.2±0.2 μmol/g, respectively; these drugs did not cause renal toxicity. Despite this, none of the adverse effects of 0.5 mM CAA was prevented by the previous in vivo administration of mesna or amifostine. Toxicity of 0.5 mM CAA to rat proximal tubules was shown by the fall of cellular adenosine triphosphate (ATP), total glutathione and coenzyme A + acetyl-coenzyme A levels and by the altered metabolic viability of renal cells. Long-term exposure of cortical slices to CAA concentrations ≥30 μM caused severe cell toxicity (i.e. decrease in cellular ATP, total glutathione, and coenzyme A + acetyl-coenzyme A levels), which was not prevented by the in vivo administration of mesna or amifostine.

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Authors and Affiliations

  1. INSERM U 820 - Métabolomique et maladies métaboliques, Faculté Laennec, 7–11 rue Paradin, 69372, Lyon Cedex 08, France

    Zeinab Yaseen, Christian Michoudet, Gabriel Baverel & Laurence Dubourg

  2. Université Claude Bernard, Lyon, France

    Zeinab Yaseen, Christian Michoudet, Gabriel Baverel & Laurence Dubourg

  3. Exploration fonctionnelle rénale et métabolique, Hôpital Edouard Herriot, Lyon, France

    Gabriel Baverel & Laurence Dubourg

Authors
  1. Zeinab Yaseen
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  2. Christian Michoudet
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  3. Gabriel Baverel
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  4. Laurence Dubourg
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Correspondence to Gabriel Baverel.

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Yaseen, Z., Michoudet, C., Baverel, G. et al. In vivo mesna and amifostine do not prevent chloroacetaldehyde nephrotoxicity in vitro. Pediatr Nephrol 23, 611–618 (2008). https://doi.org/10.1007/s00467-007-0689-6

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  • DOI: https://doi.org/10.1007/s00467-007-0689-6

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