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Human skin kinetics of cyclic depsipeptide mycotoxins

Lien Taevernier (UGent) , Lieselotte Veryser (UGent) , Nathalie Roche (UGent) and Bart De Spiegeleer (UGent)
(2014) JOURNAL OF PEPTIDE SCIENCE. 20(suppl. 1). p.S299-S300
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Abstract
Cyclic depsipeptides (CDPs) are an emerging group of naturally occurring bioactive peptides, some of which are already developed as pharmaceutical drugs, e.g. valinomycin. They are produced by bacteria, marine organisms and fungi [1]. Some CDPs are secondary fungal metabolites, which can be very toxic to humans and animals, and are therefore called mycotoxins. Currently, dermal exposure data of CDP mycotoxins is scarce and fragmentary with a lack of understanding about the local skin and systemic kinetics and effects, despite their widespread skin contact and intrinsic hazard. Moreover, mechanistic pathways and models are completely absent. Therefore our general goal was to provide a quantitative characterisation of their dermal kinetics. The emerging cyclic depsipeptide mycotoxins enniatins (ENNs) and beauvericin (BEA) were used as model compounds and their transdermal kinetics were quantitatively evaluated using human skin in an in vitro Franz diffusion cell set-up and UPLC-MS analytics [2]. BEA and ENNs are non-ionised cyclic hexadepsipeptides, with ionophoric and lipophilic properties, causing serious health problems [3-6]. Overall, immunosuppressive effects are thought to play a role in their toxicity. This knowledge is needed not only for the risk assessment due to skin-contact of CDP-contaminated food, feed, indoor surfaces and airborne particles, but also for the development of topically applied drugs with CDP-like structure, treating dermatological diseases or having systemic functions after transdermal penetration. References: [1] R. Lemmens-Gruber, M.R. Kamyar, R. Dornetshuber, Current Medicinal Chemistry, 16, 1122 (2009). [2] L. Taevernier, L. Veryser, N. Roche, S. Vansteelandt, B. De Spiegeleer, manuscript in preparation. [3] M. Jestoi, Critical Reviews in Food Science and Nutrition, 48, 21 (2008). [4] M. Celik, H. Aksoy, S.Yilmaz, Ecotoxicology and Environmental Safety, 73, 1553 (2010). [5] R. Dornetshuber, P. Heffeter, M.R. Kamyar, Chemical Research in Toxicology, 20, 465 (2007). [6] A. Tonshin, V. Teplova, M. Andersson, Toxicology, 276, 49 (2010).
Keywords
cyclic depsipeptides, mycotoxins, beauvericin, risk assessment, enniatins, skin kinetics

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Chicago
Taevernier, Lien, Lieselotte Veryser, Nathalie Roche, and Bart De Spiegeleer. 2014. “Human Skin Kinetics of Cyclic Depsipeptide Mycotoxins.” In Journal of Peptide Science, 20:S299–S300.
APA
Taevernier, L., Veryser, L., Roche, N., & De Spiegeleer, B. (2014). Human skin kinetics of cyclic depsipeptide mycotoxins. JOURNAL OF PEPTIDE SCIENCE (Vol. 20, pp. S299–S300). Presented at the 33rd European Peptide symposium.
Vancouver
1.
Taevernier L, Veryser L, Roche N, De Spiegeleer B. Human skin kinetics of cyclic depsipeptide mycotoxins. JOURNAL OF PEPTIDE SCIENCE. 2014. p. S299–S300.
MLA
Taevernier, Lien et al. “Human Skin Kinetics of Cyclic Depsipeptide Mycotoxins.” Journal of Peptide Science. Vol. 20. 2014. S299–S300. Print.
@inproceedings{5838710,
  abstract     = {Cyclic depsipeptides (CDPs) are an emerging group of naturally occurring bioactive peptides, some of which are already developed as pharmaceutical drugs, e.g. valinomycin. They are produced by bacteria, marine organisms and fungi [1]. Some CDPs are secondary fungal metabolites, which can be very toxic to humans and animals, and are therefore called mycotoxins. Currently, dermal exposure data of CDP mycotoxins is scarce and fragmentary with a lack of understanding about the local skin and systemic kinetics and effects, despite their widespread skin contact and intrinsic hazard. Moreover, mechanistic pathways and models are completely absent.
Therefore our general goal was to provide a quantitative characterisation of their dermal kinetics. The emerging cyclic depsipeptide mycotoxins enniatins (ENNs) and beauvericin (BEA) were used as model compounds and their transdermal kinetics were quantitatively evaluated using human skin in an in vitro Franz diffusion cell set-up and UPLC-MS analytics [2]. BEA and ENNs are non-ionised cyclic hexadepsipeptides, with ionophoric and lipophilic properties, causing serious health problems [3-6]. Overall, immunosuppressive effects are thought to play a role in their toxicity.
This knowledge is needed not only for the risk assessment due to skin-contact of CDP-contaminated food, feed, indoor surfaces and airborne particles, but also for the development of topically applied drugs with CDP-like structure, treating dermatological diseases or having systemic functions after transdermal penetration.
References:
[1] R. Lemmens-Gruber, M.R. Kamyar, R. Dornetshuber, Current Medicinal Chemistry, 16, 1122 (2009).
[2] L. Taevernier, L. Veryser, N. Roche, S. Vansteelandt, B. De Spiegeleer, manuscript in preparation.
[3] M. Jestoi, Critical Reviews in Food Science and Nutrition, 48, 21 (2008).
[4] M. Celik, H. Aksoy, S.Yilmaz, Ecotoxicology and Environmental Safety, 73, 1553 (2010).
[5] R. Dornetshuber, P. Heffeter, M.R. Kamyar, Chemical Research in Toxicology, 20, 465 (2007).
[6] A. Tonshin, V. Teplova, M. Andersson, Toxicology, 276, 49 (2010).},
  articleno    = {abstract P303},
  author       = {Taevernier, Lien and Veryser, Lieselotte and Roche, Nathalie and De Spiegeleer, Bart},
  booktitle    = {JOURNAL OF PEPTIDE SCIENCE},
  issn         = {1075-2617},
  keywords     = {cyclic depsipeptides,mycotoxins,beauvericin,risk assessment,enniatins,skin kinetics},
  language     = {eng},
  location     = {Sofia, Bulgaria},
  number       = {suppl. 1},
  pages        = {abstract P303:S299--abstract P303:S300},
  title        = {Human skin kinetics of cyclic depsipeptide mycotoxins},
  volume       = {20},
  year         = {2014},
}

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