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New insights into the organ-specific adverse effects of fumonisin B1: comparison between lung and liver

  • Organ Toxicity and Mechanisms
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Abstract

Fumonisin B1 (FB1) is a well-known inhibitor of de novo sphingolipid biosynthesis, due to its ability to inhibit ceramide synthases (CerS) activity. In mammals, this toxin triggers broad clinical symptoms with multi-organ dysfunction such as hepatotoxicity or pulmonary edema. The molecular mechanism of CerS inhibition by FB1 remains unknown. Due to the existence of six mammalian CerS isoforms with a tissue-specific expression pattern, we postulated that the organ-specific adverse effects of FB1 might be due to different CerS isoforms. The sphingolipid contents of lung and liver were compared in normal and FB1-exposed piglets (gavage with 1.5 mg FB1/kg body weight daily for 9 days). The effect of the toxin on each CerS was deduced from the analysis of its effects on individual ceramide (Cer) and sphingomyelin (SM) species. As expected, the total Cer content decreased by half in the lungs of FB1-exposed piglets, while in contrast, total Cer increased 3.5-fold in the livers of FB1-exposed animals. Our data also indicated that FB1 is more prone to bind to CerS4 and CerS2 to deplete lung and to enrich liver in d18:1/C20:0 and d18:1/C22:0 ceramides. It also interact with CerS1 to enrich liver in d18:1/C18:0 ceramides. Cer levels were counterbalanced by those of SM. In conclusion, these results demonstrate that the specificity of the effects of FB1 on tissues and organs is due to the effects of the toxin on CerS4, CerS2, and CerS1.

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Acknowledgments

This study was supported by the Région Midi-Pyrénées, France. We thank Prof. John Woodley for careful editing and critical reading of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. INRA, UMR1331 Toxalim, Research Centre in Food Toxicology, 31027, Toulouse, France

    Nicolas Loiseau, Arnaud Polizzi, Mirindra Rakotonirainy, Jennifer Loy, Jean-Luc Viadere, Anne-Marie Cossalter, Jean-Denis Bailly, Olivier Puel, Martine Kolf-Clauw, Hervé Guillou & Isabelle P. Oswald

  2. ENVT, INP, UMR1331 Toxalim, Université de Toulouse, 31076, Toulouse, France

    Nicolas Loiseau, Arnaud Polizzi, Mirindra Rakotonirainy, Jennifer Loy, Jean-Luc Viadere, Anne-Marie Cossalter, Jean-Denis Bailly, Olivier Puel, Martine Kolf-Clauw, Hervé Guillou & Isabelle P. Oswald

  3. INSERM, U1048, MetaToul-Lipidomic Core Facility, Université Paul Sabatier, Toulouse, France

    Aude Dupuy & Justine Bertrand-Michel

  4. INSERM, UMR1037, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France

    Nicole Therville & Thierry Levade

  5. ToxAlim, UMR1331, Integrative Toxicology and Metabolism Group, INRA/INPT/UPS, 180 Chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France

    Nicolas Loiseau

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  1. Nicolas Loiseau
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Loiseau, N., Polizzi, A., Dupuy, A. et al. New insights into the organ-specific adverse effects of fumonisin B1: comparison between lung and liver. Arch Toxicol 89, 1619–1629 (2015). https://doi.org/10.1007/s00204-014-1323-6

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