Pesticide mixture effects on liver protein abundance in HepaRG cells

Schmidt FF, Lichtenstein D, Planatscher H, Mentz A, Kalinowski J, Steinhilber AE, Joos TO, Braeuning A, Poetz O (2021)
Toxicology 458: 152839.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Schmidt, Felix F.; Lichtenstein, Dajana; Planatscher, Hannes; Mentz, AlmutUniBi; Kalinowski, JörnUniBi; Steinhilber, Andreas E.; Joos, Thomas O.; Braeuning, Albert; Poetz, Oliver
Abstract / Bemerkung
Toxicological effects of chemicals are mostly tested individually. However, consumers encounter exposure to complex mixtures, for example multiple pesticide residues, by consuming food such as crops, fruits or vegetables. Currently, more than 450 active substances are approved in the European Union, and there is little data on effects after combined exposure to several pesticides. Toxicological animal studies would increase enormously, if pesticide combinations had to be analyzed in vivo. Therefore, in vitro methods addressing this issue are needed. We have developed 32 immunoaffinity-based mass spectrometry assays to investigate the impact of hepatotoxic active substances on liver proteins in human HepaRG cells. Five compounds were selected based on their (dis) similar capability to modulate protein levels, and on their combined use in commercially available formulations. Four binary mixtures were prepared from these five substances and tested in different concentrations over three time points. We applied a novel statistical method to describe deviations from additivity and to detect antagonistic and synergistic effects. The results regarding the abundance of hepatotoxicity-related proteins showed additive behavior for 1323 out of 1427 endpoints tested, while 104 combinatorial effects deviating from additivity, such as antagonism or synergism were observed.
Stichworte
Immunoaffinity-based mass spectrometry; Pesticide mixtures; HepaRG; cells; Liver toxicity; Multiple linear regression analysis; Biomarker
Erscheinungsjahr
2021
Zeitschriftentitel
Toxicology
Band
458
Art.-Nr.
152839
ISSN
0300-483X
Page URI
https://pub.uni-bielefeld.de/record/2957069

Zitieren

Schmidt FF, Lichtenstein D, Planatscher H, et al. Pesticide mixture effects on liver protein abundance in HepaRG cells. Toxicology . 2021;458: 152839.
Schmidt, F. F., Lichtenstein, D., Planatscher, H., Mentz, A., Kalinowski, J., Steinhilber, A. E., Joos, T. O., et al. (2021). Pesticide mixture effects on liver protein abundance in HepaRG cells. Toxicology , 458, 152839. https://doi.org/10.1016/j.tox.2021.152839
Schmidt, F. F., Lichtenstein, D., Planatscher, H., Mentz, A., Kalinowski, J., Steinhilber, A. E., Joos, T. O., Braeuning, A., and Poetz, O. (2021). Pesticide mixture effects on liver protein abundance in HepaRG cells. Toxicology 458:152839.
Schmidt, F.F., et al., 2021. Pesticide mixture effects on liver protein abundance in HepaRG cells. Toxicology , 458: 152839.
F.F. Schmidt, et al., “Pesticide mixture effects on liver protein abundance in HepaRG cells”, Toxicology , vol. 458, 2021, : 152839.
Schmidt, F.F., Lichtenstein, D., Planatscher, H., Mentz, A., Kalinowski, J., Steinhilber, A.E., Joos, T.O., Braeuning, A., Poetz, O.: Pesticide mixture effects on liver protein abundance in HepaRG cells. Toxicology . 458, : 152839 (2021).
Schmidt, Felix F., Lichtenstein, Dajana, Planatscher, Hannes, Mentz, Almut, Kalinowski, Jörn, Steinhilber, Andreas E., Joos, Thomas O., Braeuning, Albert, and Poetz, Oliver. “Pesticide mixture effects on liver protein abundance in HepaRG cells”. Toxicology 458 (2021): 152839.

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