Effects of DDT and permethrin on rat hepatocytes cultivated in microfluidic biochips: Metabolomics and gene expression study

Environmental Toxicology and Pharmacology
Rachid JellaliEric Leclerc

Abstract

Dichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are amongst most prevalent pesticides in the environment. Although their toxicity has been extensively studied, molecular mechanisms and metabolic effects remain unclear, including in liver where their detoxification occurs. Here, we used metabolomics, coupled to RT-qPCR analysis, to examine effects of DDT and PMT on hepatocytes cultivated in biochips. At 150 μM, DDT caused cell death, cytochrome P450 induction and modulation of estrogen metabolism. Metabolomics analysis showed an increase in some lipids and sugars after 6 h, and a decrease in fatty acids (tetradecanoate, octanoate and linoleate) after 24 h exposure. We also found a change in expression associated with genes involved in hepatic estrogen, lipid, and sugar metabolism. PMT at 150 μM perturbed lipid/sugar homeostasis and estrogen signaling pathway, between 2 and 6 h. After 24 h, lipids and sugars were found to decrease, suggesting continuous energy demand to detoxify PMT. Finally, at 15 μM, DDT and PMT appeared to have a small effect on metabolism and were detoxified after 24 h. Our results show a time-dependent perturbation of sugar/lipid homeostasis by DDT and PMT at 150 μM. Furthermore, DDT at high dose...Continue Reading

Citations

Apr 17, 2018·Journal of Applied Toxicology : JAT·Rachid JellaliEric Leclerc
Jul 22, 2019·Environmental Science and Pollution Research International·Jin-Zheng WangJun Wang
Jan 7, 2021·Biotechnology and Bioengineering·Mathieu DanoyEric Leclerc
Nov 6, 2020·Environmental Health : a Global Access Science Source·Jennifer L M ThorsonMichael K Skinner
Mar 30, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Rachid JellaliEric Leclerc
Jul 6, 2021·Ecotoxicology and Environmental Safety·Anouar FerianiAbdel Halim Harrath
Sep 10, 2020·Environmental Science & Technology·Jason MagnusonDaniel Schlenk

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