Hepatotoxicity study of combined exposure of DEHP and ethanol: A comprehensive analysis of transcriptomics and metabolomics.

Both di(2-ethylhexyl)phthalate (DEHP) and ethanol have toxic effects on the liver, and the oral exposure to DEHP in combination with ethanol may exist in the alcohol consumers, however, current food safety risk assessments based solely on the toxicity data of DEHP may underestimate the health impacts of phthalates, especially in population that continually consume alcoholic beverages. Here we performed a comprehensive analysis of transcriptomics and metabolomics to study if there is a synergistic effect of DEHP and ethanol on the liver of mice. We found that the expression of genes associated with lipid accumulation and oxidation elevated simultaneously when exposed to DEHP alone or combined with ethanol, based on the results of pathophysiological tests, we considered that the elevated level of lipid accumulation was more significant which caused hepatic lipid accumulation ultimately. We observed no difference in the transcriptome profiles between combined exposure group and DEHP group, but metabolites pathway enrichment analysis showed that ethanol and DEHP may have a synergistic effect on the unsaturated fatty acid metabolism. In summary, our results suggest that DEHP exposed alone or combined with ethanol caused hepatic lipid accumulation, ethanol and DEHP may have a synergistic effect on the unsaturated fatty acid metabolism.