Effects of Acute Exposure to 2-ethylhexyl Diphenyl Phosphate on Lipid Metabolism and Mitochondrial Function in Zebrafish Larvae
2-ethylhexyl diphenyl phosphate(EHDPP)is an aryl organophosphorus flame retardant,which is ubiquitously found in various environmental matrices.While previous in vitro studies have emphasized the negative impact of EHDPP on lipid metabolism,there remains a dearth of in vivo research exploring its potential toxic effects and underlying mechanisms.In the present study,zebrafish(Danio rerio)embryos(＜2 hpf)were exposed to environmentally relevant concentrations(0,1,10,100,250 and 500 μg·L-1)for 5 days.Results showed that 100,250 and 500 μg·L-1 EHDPP may lead to developmental toxicity,evidenced by the increased malformation rate,reduced hatching rate,heart rate,survival rate and body length,in comparison with the control.The levels of total cholesterol and triglycerides were significantly reduced in 500 μg·L-1 EHDPP group compared to the control,suggesting that EHDPP caused disorders of lipid metabolism.EHDPP resulted in a notable reduction in the concentrations of ATP,SOD,and GSH,along with an elevation in ROS levels,suggestive of mitochondrial dysfunction triggered by EHDPP.Upon further analysis,it was revealed that the transcription of the 18rs-rrn gene was significantly reduced,while the expressions of genes involved in mitochondrial division(including mitochondrial fission protein 1(fis1)and dynamin-related protein(drp1)),fusion(optic atrophy 1(opa1)),and autophagy(PTEN-induced putative kinase 1(pink1)and FUN14 domain containing 1(fundc1))were notably upregulated,which may partially account for the mitochondrial dysfunction.Genes involved in lipid biosynthesis including acid synthetase(fas)and apolipoprotein E(apoe)genes were significantly downregulated,whereas genes related to lipid metabolism such as peroxisome proliferators-activated receptors(pparα and pparβ)and acyl-CoA oxidase 1(acox1)were upregulated.These results implied that EHDPP may disturb fatty acid oxidation and lipid synthesis in zebrafish larvae which might result from mitochondrial dysfunction.In conclusion,our study found that EHDPP may induce lipid metabolism disorders.For the first time,we have demonstrated mitochondrial dysfunction in vivo resulting from the effects of EHDPP,potentially offering novel insights into the toxicity elicited by this compound.
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