Journal
JOURNAL OF HAZARDOUS MATERIALS
Volume 388, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jhazmat.2020.122034
Keywords
Organophosphate flame retardants; EHDPHP; Metabolic homeostasis; Dose; Diet
Categories
Funding
- National Key Research and Development Program of China [2016YFD0200202]
- National Natural Science Foundation of China [21337005]
- Young Elite Scientists Sponsorship Program by CAST
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The environmental health risks of a new type of organophosphate flame retardant, 2-ethylhexyl diphenyl phosphate (EHDPHP), which is present in large quantities in various Nordic foods, have attracted the attention of scientists recently. In this study, the metabolic homeostasis of low-fat diet (LFD) and high-fat diet (HFD) fed male mice offspring was assessed after perinatal exposure to two doses (30 mu g/kg bw/day and 300 mu g/kg bw/day) of EHDPHP. Perinatal exposure to EHDPHP resulted in weight changes in male mice offspring, altered glucose tolerance and induced liver damage, and surprisingly these changes were dose- and diet-specific. Then the H-1 NMR-based metabolomics, 16S rRNA sequencing, and qRT-PCR techniques were used to explore the mechanisms of these specific changes. The results indicate that the increase in short-chain fatty acids and the increase in Clostridium in the high-dose group may be responsible for the dose-specificity, while the attenuation of the purine metabolic pathway and the decrease in glutamine levels in the HFD group are accountable for the dietspecificity. In addition, down-regulation of PPARG (peroxisome proliferator-activated receptor gamma) gene expression levels might have caused the decrease in body weight in the H + HFD (high dose exposure with HFD feeding) group. Over all, these results elucidated the effects of dosage and diet on the toxicology of EHDPHP.
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