Transcriptomic analysis of hepatotoxicity induced by pesticides imazalil, thiacloprid and clothianidin alone or in binary mixtures in a 28-day study in female Wistar rats
Co-occurrence of pesticide residues in food commodities raises a safety issue as their mixture effects on human health is largely unknown and need to be investigated. In a previous study, we reported the toxicological effects (pathology & histopathology) of imazalil (IMZ), thiacloprid (THI), and clothianidin (CTD) alone and in binary mixtures in a 28-day gavage study in female Wistar rats. Here, we undertook a transcriptomic analysis by means of total RNA sequencing (RNA-Seq). Ingenuity pathway analysis (IPA) was used to gain mechanistic information on the hepatotoxic pathways affected after treatment with pesticides, alone and in mixtures. Our data shows that 2986 genes were deregulated by CTD while IMZ and THI had effect on 194 and 225 genes, respectively. All three compounds share a common subset of genes whose network is associated with xenobiotic metabolism and nuclear receptors. Additionally, DNA repair process was predicted for CTD. The same networks were retrieved for the mixtures.  Dose addition was indicated for the evaluated gene expressions. Our results bring new insight in the hepatotoxicity mechanisms of IMZ, THI, and CTD. Overall design: RNA sequencing of 31 liver samples, treatment of rats with three pesticides (imazalil, thiacloprid and clothianidin) and their binary mixtures