Evaluation of the Toxic Effects of Municipal Wastewater Effluent on Mice Using Omic Approaches

Zhang, Yan; Huang, Kailong; Deng, Yongfeng; Zhao, Yanping; Wu, Bing; Xu, Ke; Ren, Hongqiang

doi:10.1021/es401615y

Cited by 22 publications

(13 citation statements)

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“…NMR spectra were processed (phase correction, baseline correction and ppm shift correction using trisilylpropionic acid [TSP] or tetramethylsilane [TMS]) and analyzed (GSD, Global Spectral Deconvolution) using MestReNova v6.1.0–6224 software. Metabolite resonances were identified using both Chenomx NMR Suite 8.02 and published literature 31 32 33 . NMR spectra and assigned metabolites are presented in Figure S1 , Figure S2 and Table S1 .…”

Section: Methodsmentioning

confidence: 99%

TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

Zhang

Wang

et al. 2016

Sci Rep

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104

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Triphenyl phosphate is a high production volume organophosphate flame retardant that has been detected in multiple environmental media at increasing concentrations. The environmental and health risks of triphenyl phosphate have drawn attention because of the multiplex toxicity of this chemical compound. However, few studies have paid close attention to the impacts of triphenyl phosphate on liver metabolism. We investigated hepatic histopathological, metabolomic and transcriptomic responses of zebrafish after exposure to 0.050 mg/L and 0.300 mg/L triphenyl phosphate for 7 days. Metabolomic analysis revealed significant changes in the contents of glucose, UDP-glucose, lactate, succinate, fumarate, choline, acetylcarnitine, and several fatty acids. Transcriptomic analysis revealed that related pathways, such as the glycosphingolipid biosynthesis, PPAR signaling pathway and fatty acid elongation, were significantly affected. These results suggest that triphenyl phosphate exposure markedly disturbs hepatic carbohydrate and lipid metabolism in zebrafish. Moreover, DNA replication, the cell cycle, and non-homologous end-joining and base excision repair were strongly affected, thus indicating that triphenyl phosphate hinders the DNA damage repair system in zebrafish liver cells. The present study provides a systematic analysis of the triphenyl phosphate-induced toxic effects in zebrafish liver and demonstrates that low concentrations of triphenyl phosphate affect normal metabolism and cell cycle.

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Section: Methodsmentioning

confidence: 99%

TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

Zhang

Wang

et al. 2016

Sci Rep

Self Cite

104

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“…In recent years, the combinations of gas chromatography-quadrupole time of flight mass spectrometry (GC-Q-TOF/MS) and liquid chromatography-quadrupole time of flight mass spectrometry (LC-Q-TOF/MS) have been applied successfully in numerous metabolomics studies to achieve more sensitive and accurate metabolic profiling and screening of biomarkers [15]. For instance, Zhang et al employed NMR-based metabolomics to study the toxic effects of municipal wastewater effluent in mice and found that municipal wastewater effluent induced amino acid, nucleotide, lipid, and energy metabolism perturbations, which result in hepatotoxicity and nephrotoxicity in mice [16]. Xu et al adopted 1 H-NMR based metabolomics to study the toxic effects of butachlor on gold fish and found that metabolic pathways related to oxidative stress, energy metabolism, amino acids metabolism, and neurotransmitter balance were significantly perturbed after butachlor exposure [17].…”

Section: Introductionmentioning

confidence: 99%

Identifying Metabolic Perturbations and Toxic Effects of Rac-Metalaxyl and Metalaxyl-M in Mice Using Integrative NMR and UPLC-MS/MS Based Metabolomics

Zhang

et al. 2019

IJMS

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Although metabolic perturbations are sensitive indicators for low-dose toxic effects, the metabolic mechanisms affected by rac-metalaxyl and metalaxyl-M in mammals from a metabolic profiling perspective remain unclear. In this study, the metabolic perturbations and toxic effects of rac-metalaxyl and metalaxyl-M in mice were carefully investigated using integrative nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based metabolomics. Histopathology, NMR-based untargeted urine profile, multivariate pattern recognition, metabolite identification, pathway analysis, UPLC-MS/MS based targeted serum amino acids, and tryptophan pathway analysis were determined after rac-metalaxyl and metalaxyl-M exposure, individually. Histopathology indicated that metalaxyl-M induced greater hepatocellular inflammatory, necrosis, and vacuolation in mice than rac-metalaxyl at the same exposure dosage. The metabolic perturbations induced by rac-metalaxyl and metalaxyl-M were directly separated using partial least-squares discriminant analysis (PLS-DA). Furthermore, metabolite identification and pathway analysis indicated that rac-metalaxyl mainly induced ten urine metabolite changes and four pathway fluctuations. However, metalaxyl-M induced 19 urine metabolite changes and six pathway fluctuations. Serum amino acids and tryptophan pathway metabolite changes induced by rac-metalaxyl and metalaxyl-M were also different even at the same exposure level. Such results may provide specific insight into the metabolic perturbations and toxic effects of rac-metalaxyl and metalaxyl-M, and contribute to providing available data for health risk assessments of rac-metalaxyl and metalaxyl-M at a metabolomics level.

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“…These advantages prompted the use of toxicogenomics to test the effect of single molecules or simple chemical mixtures [ 8 , 9 ]. The objectives of transcriptomics in environmental studies (ecotoxicogenomics) are the accomplishment of classical toxicological and new molecular endpoints in the identification of exposure-related alterations, and proper consideration of the complex nature of anthropogenic pollution and bioaccumulation events [ 10 – 17 ]. Besides environments are frequently contaminated with multiple classes of compounds, only a limited number of toxicological studies have recently addressed this problem by using omics approaches to fish species, in environmental field [ 11 , 18 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this process, the integration of toxicogenomics data from different models is pivotal to validate deregulated patterns, to challenge the low signal to noise ratio and to predict potential risks for human health [ 23 , 24 ]. Mouse and zebrafish studies indicate that gene expression profile approaches are successful in identifying chemical-specific patterns of altered gene expression [ 2 , 25 – 27 ]; for this reason, and for their genetics and biology, these models are widely accepted by the scientific community for environmental toxicology studies [ 10 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Cross-species toxicogenomic analyses and phenotypic anchoring in response to groundwater low-level pollution

et al. 2014

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BackgroundComparison of toxicogenomic data facilitates the identification of deregulated gene patterns and maximizes health risk prediction in human.ResultsHere, we performed phenotypic anchoring on the effects of acute exposure to low-grade polluted groundwater using mouse and zebrafish. Also, we evaluated two windows of chronic exposure in mouse, starting in utero and at the end of lactation. Bioinformatic analysis of livers microarray data showed that the number of deregulated biofunctions and pathways is higher after acute exposure, compared to the chronic one. It also revealed specific profiles of altered gene expression in all treatments, pointing to stress response/mitochondrial pathways as major players of environmental toxicity. Of note, dysfunction of steroid hormones was also predicted by bioinformatic analysis and verified in both models by traditional approaches, serum estrogens measurement and vitellogenin mRNA determination in mice and zebrafish, respectively.ConclusionsIn our report, phenotypic anchoring in two vertebrate model organisms highlights the toxicity of low-grade pollution, with varying susceptibility based on exposure window. The overlay of zebrafish and mice deregulated pathways, more than single genes, is useful in risk identification from chemicals implicated in the observed effects.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1067) contains supplementary material, which is available to authorized users.

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Evaluation of the Toxic Effects of Municipal Wastewater Effluent on Mice Using Omic Approaches

Cited by 22 publications

References 50 publications

TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

Identifying Metabolic Perturbations and Toxic Effects of Rac-Metalaxyl and Metalaxyl-M in Mice Using Integrative NMR and UPLC-MS/MS Based Metabolomics

Cross-species toxicogenomic analyses and phenotypic anchoring in response to groundwater low-level pollution

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