The organochlorine
dieldrin (DLD) bioaccumulates in
lipid-rich tissues and is associated with immunosuppression, altered metabolism, and
cancer. The objective of this study was to determine the effect of DLD on the hepatic
proteome in zebrafish following dietary treatment as the liver is central to metabolism. Females were fed a control dose or one of three doses of DLD-contaminated food pellets over 21 days. Both label-free and iTRAQ proteomics were conducted as two complementary methods to expand coverage of the
proteome. Label-free proteomics quantified 1563
proteins: 6
proteins showed a linear dose-response with DLD. iTRAQ quantified >3500
proteins; 5
proteins were decreased and 34
proteins were increased in abundance within the liver with all three doses. Overall, DLD reduced the abundance of
proteins associated with
glucose and
cholesterol metabolism, lipid oxidation, liver function, and immune-related processes. Few
proteins were identified by both methods as being altered (~1%), suggesting that each method detected different subsets of
proteins.
Protein responses in the liver were largely dependent on dose, however
proteins related to liver and organ function, centrosome separation,
glucose/energy metabolism, and immune-related pathways were confirmed by each independent technique and were suppressed with DLD exposure. This study identifies proteomic responses that are associated with organochlorine-induced hepatotoxicity. BIOLOGICAL SIGNIFICANCE: Environmental contaminants cause hepatotoxicity because the liver is the major organ for detoxification. The legacy
pesticide dieldrin significantly bioaccumulates in tissues, and can affect molecular processes that can lead to liver pathology. LC MS/MS proteomics identified
protein networks related to
tumors, energy homeostasis, and chromosomal separation as those affected by dietary exposure to
dieldrin. We applied two orthogonal mass spectrometry-based methods to more completely survey the liver
proteome, strengthening data interpretation. These data improve understanding as to the effects of organochlorine
pesticide toxicity in the liver and the study identifies
proteome networks that can contribute to adverse outcome pathways for
pesticide exposure.