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In vivo comparison of the proangiogenic properties of chlordecone and three of its dechlorinated derivatives formed by in situ chemical reduction

  • Eid Alabed Alibrahim
  • Samuel LegeayEmail author
  • Pierre-André Billat
  • Emmanuelle Bichon
  • Ingrid Guiffard
  • Jean-Philippe Antignac
  • Pierre Legras
  • Jérôme Roux
  • Sébastien Bristeau
  • Nicolas Clere
  • Sébastien Faure
  • Christophe Mouvet
Environmental and human health issues related to long term contamination by chlordecone in the French West Indies
  • 14 Downloads

Abstract

In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by chlordecone (CLD). Evidences provided by the literature indicate an association between the development of prostate cancer and CLD exposure (Multigner et al. 2010). In a previous in vitro study, we demonstrated that the two main dechlorinated CLD derivatives formed by ISCR, CLD-1Cl, and CLD-3Cl have lower cytotoxicity and proangiogenic properties than CLD itself (Legeay et al. 2017). By contrast, nothing is known on the in vivo proangiogenic effect of these dechlorinated derivatives. Based on in vitro data, the aims of this study were therefore to evaluate the in vivo influence of CLD and three of its dechlorinated metabolites in the control of neovascularization in a mice model of prostate cancer. The proangiogenic effect of CLD and three of its dechlorinated derivatives, CLD-1Cl, CLD-3Cl, and CLD-4Cl, was evaluated on a murine model of human prostate tumor (PC-3) treated, at two exposure levels: 33 μg/kg and 1.7 μg/kg respectively reflecting acute and chronic toxic exposure in human. The results of serum measurements show that, for the same ingested dose, the three metabolite concentrations were significantly lower than that of CLD. Dechlorination of CLD lead therefore to molecules that are biologically absorbed or metabolized, or both, faster than the parent molecule. Prostate tumor growth was lower in the groups treated by the three metabolites compared to the one treated by CLD. The vascularization measured on the tumor sections was inversely proportional to the rate of dechlorination, the treatment with CLD-4Cl showing no difference with control animals treated with only the vehicle oil used for all substances tested. We can therefore conclude that the proangiogenic effect of CLD is significantly decreased following the ISCR-resulting dechlorination. Further investigations are needed to elucidate the molecular mechanisms by which dechlorination of CLD reduces proangiogenic effects in prostate tumor.

Keywords

In situ chemical reduction Chlordecone Dechlorination Angiogenesis Prostate cancer 

Notes

Funding information

The results presented here were obtained through financing by the French Ministry of Environment, General Directorate for Risk Prevention (action F of the 2015 grant program MEDDE/BRGM).

Compliance with ethical standards

All animal procedures listed in this article were performed as per the protocol approved by the local ethic committees (Angers, France; protocol APAFIS #5872) and the number of animals was limited regarding animal ethics.

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Eid Alabed Alibrahim
    • 1
  • Samuel Legeay
    • 1
    Email author
  • Pierre-André Billat
    • 1
  • Emmanuelle Bichon
    • 2
  • Ingrid Guiffard
    • 2
  • Jean-Philippe Antignac
    • 2
  • Pierre Legras
    • 3
  • Jérôme Roux
    • 3
  • Sébastien Bristeau
    • 4
  • Nicolas Clere
    • 1
  • Sébastien Faure
    • 1
  • Christophe Mouvet
    • 5
  1. 1.MINT, UNIV Angers, INSERM 1066, CNRS 6021Université Bretagne LoireAngersFrance
  2. 2.Laboratoire d’Etude des Résidus et Contaminants dans les Aliments (LABERCA), Oniris, INRAUniversité Bretagne LoireNantesFrance
  3. 3.SCAHU, UNIV Angers, Pavillon Ollivier, UFR Sciences médicalesAngersFrance
  4. 4.Laboratory DivisionBRGMOrléans, Cedex 2France
  5. 5.Water, Environment and Ecotechnologies DivisionBRGMOrléans, Cedex 2France

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