Abstract

The aim of this study was to elucidate how vitamin E (alpha tocopherol) may ameliorate the toxicity of the pesticide chlorpyrifos in Atlantic salmon. Freshly isolated hepatocytes were exposed to vitamin E, chlorpyrifos or a combination of vitamin E and chlorpyrifos (all 100 μM). Transcriptomics (RNA-seq) and metabolomics were used to screen for effects of vitamin E and chlorpyrifos. By introducing vitamin E, the number of upregulated transcripts induced by chlorpyrifos exposure was reduced from 941 to 626, while the number of downregulated transcripts was reduced from 901 to 742 compared to the control. Adding only vitamin E had no effect on the transcriptome. Jak-STAT signaling was the most significantly affected pathway by chlorpyrifos treatment according to the transcriptomics data. The metabolomics data showed that accumulation of multiple long chain fatty acids and dipeptides and amino acids in chlorpyrifos treated cells was partially alleviated by vitamin E treatment. Significant interaction effects between chlorpyrifos and vitamin E were seen for 15 metabolites, including 12 dipeptides. The antioxidant had relatively modest effects on chlorpyrifos-induced oxidative stress. By combining the two data sets, the study suggests that vitamin E supplementation prevents uptake and accumulation of fatty acids, and counteracts inhibited carbohydrate metabolism. Overall, this study shows that vitamin E only to a moderate degree modifies chlorpyrifos toxicity in Atlantic salmon liver cells.

Highlights

  • Several nutrients have modifying effects on the toxicity of contaminants

  • This work shows that alpha tocopherol to a modest degree can affect chlorpyrifos toxicity in Atlantic salmon liver cells

  • The cellular response as predicted by the metabolite outcome suggests that the main effects of chlorpyrifos exposure were on energy metabolism, lipid metabolism, BCAA/glutathione metabolism and nucleotide metabolism

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Summary

Introduction

Several nutrients have modifying effects on the toxicity of contaminants. Vitamin E (tocopherols), flavonoids, and fatty acids amend the toxicity of polycyclic aromatic hydrocarbons (PAHs) and pesticides [1,2,3]. The mechanisms underlying such interactions are often not very well characterized. Interactions between nutrients and contaminants are of particular interest in fish, and especially in farmed fish such as Atlantic salmon, with the recent replacement of fish-based feed ingredients with plant-based feed ingredients.

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