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As persistent organic pollutants, polychlorinated biphenyls (PCBs) accumulate in the bodies of animals and humans, resulting in toxic effects on the reproductive, immune, nervous, and endocrine systems. The biological and toxicological characteristics of enantiomers of chiral PCBs may differ, but these enantioselective effects of PCBs have not been fully characterized. In this study, we performed metabolomics analysis, using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to investigate the enantioselective toxic effects of PCB95 in zebrafish (Danio rerio) embryos after exposure to three dose levels of 0.1, 1, and 10 μg/L for 72 h. Multivariate analysis directly reflected the metabolic perturbations caused by PCB95. The effects of (-)-PCB95 and (+)-PCB95 were more prominent than those of the racemate in zebrafish embryos. A total of 26 endogenous metabolites were selected as potential marker metabolites with variable importance at projection values larger than 1 and significant differences (p<0.05). These metabolites included amino acids, organic acids, nucleosides, betaine, and choline. The changes in these biomarkers were dependent on the enantiomer-specific structures of PCB95. Fifteen metabolic pathways were significantly affected, and several nervous and immune system-related metabolites were significantly validated after exposure. These metabolic changes indicated that the toxic effects of PCB95 may be associated with the interaction of PCB95 with the nervous and immune systems, thus resulting in disruption of energy metabolism and liver function. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Pulsatilla chinensis (Bunge) Regel is a valuable traditional Chinese medicine (TCM) which is widely used for the treatment of schistosomiasis, inflammatory, bacterial infections. In recent years, P chinensis has been reported to exhibit antitumor activities. However, the mechanisms underlying its toxic effects remain largely unresolved. This paper is designed to investigate the damage of long-term oral P. chinensis saponins (PRS) and to explore its potential damage mechanisms by serum metabonomics approach. Materials and methods The serum samples from control and PRS treated rats were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) in positive ionization mode and negative ionization mode. Liver function index of ALT, AST and ALP, blood biochemistry and biomarkers were examined to identify specific changes of injury. Acquired data were subjected to principal component analysis (PCA) for differentiating the control and PRS treated groups. Then, serum metabolic profiling was analyzed and pathway analysis performed on the biomarkers reversed after PRS treated and further integration of metabolic networks. Results The results suggested that serum liver function indexes of ALT had significantly changed and stage increased. AST, ALP detection content show volatility changes. Changes in the 15 biomarkers found in the serum, such as acetaminophen glucuronide, 9 E, 11 E-linoleic acid, chenodeoxycholic acid, monoacylglycerides, sphingomyelin (SM), 7-ketodeoxycholic acid and 12-keto-deoxycholic acid, which were closely related to changes in liver injury. It could be seen clearly that with the change of the dosing time, the biomarkers in the serum have undergone obvious, regular and progressive changes through the score plot and corresponding loading plot. The underlying regulations of PRS-perturbed metabolic pathways were discussed according to the identified metabolites. Conclusion The present study proves the potential of UPLC-QTOF-MS based metabonomics in mapping metabolic response. Long-term oral administration of P. chinensis saponins can cause chronic liver injury, and its safety needs further attention. It is of great significance in safeguarding human health to explore the damage mechanism of Pulsatilla chinensis saponins on liver by serum metabolomics. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]