An eight-compound mixture but not corresponding concentrations of individual chemicals induces triglyceride accumulation in human liver cells

Lichtenstein D, Lasch A, Alarcan J, Mentz A, Kalinowski J, Schmidt FF, Poetz O, Marx-Stoelting P, Braeuning A (2021)
Toxicology 459: 152857.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Lichtenstein, Dajana; Lasch, Alexandra; Alarcan, Jimmy; Mentz, AlmutUniBi; Kalinowski, JörnUniBi; Schmidt, Felix F.; Poetz, Oliver; Marx-Stoelting, Philip; Braeuning, Albert
Abstract / Bemerkung
In real life, organisms are exposed to complex mixtures of chemicals at low concentration levels, whereas research on toxicological effects is mostly focused on single compounds at comparably high doses. Mixture effects deviating from the assumption of additivity, especially synergistic effects, are of concern. In an adverse outcome pathway (AOP)-guided manner, we analyzed the accumulation of triglycerides in human HepaRG liver cells by a mixture of eight steatotic chemicals (amiodarone, benzoic acid, cyproconazole, flusilazole, imazalil, prochloraz, propiconazole and tebuconazole), each present below its individual effect concentration at 1-3 mu M. Pronounced and significantly enhanced triglyceride accumulation was observed with the mixture, and similar effects were seen at the level of pregnane-X-receptor activation, a molecular initiating event leading to hepatic steatosis. Transcript pattern analysis indicated subtle pro-steatotic changes at low compound concentrations, which did not exert measurable effects on cellular triglycerides. Mathematical modeling of mixture effects indicated potentially more than additive behavior using a model for compounds with similar modes of action. The present data underline the usefulness of AOP-guided in vitro testing for the identification of mixture effects and highlight the need for further research on chemical mixtures and harmonization of data interpretation of mixture effects.
Stichworte
Hepatotoxicity; Pregnane-X-receptor; Steatosis; Liver
Erscheinungsjahr
2021
Zeitschriftentitel
Toxicology
Band
459
Art.-Nr.
152857
ISSN
0300-483X
Page URI
https://pub.uni-bielefeld.de/record/2957077

Zitieren

Lichtenstein D, Lasch A, Alarcan J, et al. An eight-compound mixture but not corresponding concentrations of individual chemicals induces triglyceride accumulation in human liver cells. Toxicology. 2021;459: 152857.
Lichtenstein, D., Lasch, A., Alarcan, J., Mentz, A., Kalinowski, J., Schmidt, F. F., Poetz, O., et al. (2021). An eight-compound mixture but not corresponding concentrations of individual chemicals induces triglyceride accumulation in human liver cells. Toxicology, 459, 152857. https://doi.org/10.1016/j.tox.2021.152857
Lichtenstein, D., Lasch, A., Alarcan, J., Mentz, A., Kalinowski, J., Schmidt, F. F., Poetz, O., Marx-Stoelting, P., and Braeuning, A. (2021). An eight-compound mixture but not corresponding concentrations of individual chemicals induces triglyceride accumulation in human liver cells. Toxicology 459:152857.
Lichtenstein, D., et al., 2021. An eight-compound mixture but not corresponding concentrations of individual chemicals induces triglyceride accumulation in human liver cells. Toxicology, 459: 152857.
D. Lichtenstein, et al., “An eight-compound mixture but not corresponding concentrations of individual chemicals induces triglyceride accumulation in human liver cells”, Toxicology, vol. 459, 2021, : 152857.
Lichtenstein, D., Lasch, A., Alarcan, J., Mentz, A., Kalinowski, J., Schmidt, F.F., Poetz, O., Marx-Stoelting, P., Braeuning, A.: An eight-compound mixture but not corresponding concentrations of individual chemicals induces triglyceride accumulation in human liver cells. Toxicology. 459, : 152857 (2021).
Lichtenstein, Dajana, Lasch, Alexandra, Alarcan, Jimmy, Mentz, Almut, Kalinowski, Jörn, Schmidt, Felix F., Poetz, Oliver, Marx-Stoelting, Philip, and Braeuning, Albert. “An eight-compound mixture but not corresponding concentrations of individual chemicals induces triglyceride accumulation in human liver cells”. Toxicology 459 (2021): 152857.

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