Refine search
Results 1-10 of 21
High-resolution metabolomics of exposure to tobacco smoke during pregnancy and adverse birth outcomes in the Atlanta African American maternal-child cohort
2022
Tan, Youran | Barr, Dana Boyd | Ryan, P Barry | Fedirko, Veronika | Sarnat, Jeremy A. | Gaskins, Audrey J. | Chang, Che-Jung | Tang, Ziyin | Marsit, Carmen J. | Corwin, Elizabeth J. | Jones, Dean P. | Dunlop, Anne L. | Liang, Donghai
Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014–2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed by an untargeted HRM workflow using generalized linear models, followed by pathway enrichment analysis and chemical annotation, with a meet-in-the-middle approach. The median maternal urinary cotinine concentrations were 5.93 μg/g creatinine and 3.69 μg/g creatinine in early and late pregnancy, respectively. In total, 16,481 and 13,043 metabolic features were identified in serum samples at each visit from positive and negative electrospray ionization modes, respectively. Twelve metabolic pathways were found to be associated with both cotinine concentrations and adverse birth outcomes during early and late pregnancy, including tryptophan, histidine, urea cycle, arginine, and proline metabolism. We confirmed 47 metabolites associated with cotinine levels, preterm birth, and shorter gestational age, including glutamate, serine, choline, and taurine, which are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes. The metabolic perturbations associated with cotinine levels were related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. The findings will support the further understanding of potential internal responses in association with tobacco smoke exposures, especially among African American women who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes.
Show more [+] Less [-]Bioconcentration and developmental neurotoxicity of novel brominated flame retardants, hexabromobenzene and pentabromobenzene in zebrafish
2021
Chen, Xiangping | Guo, Wei | Lei, Lei | Guo, Yongyong | Yang, Lihua | Han, Jian | Zhou, Bingsheng
The flame retardants hexabromobenzene (HBB) and pentabromobenzene (PBB) have been extensively used and become ubiquitous pollutants in the aquatic environment and biota, but their potential toxic effects on wildlife remained unknown. In this study, by using zebrafish (Danio rerio) as a model, the bioconcentration and developmental neurotoxicity were investigated. Zebrafish embryos were exposed to HBB and PBB (0, 30, 100 and 300 μg/L) from 2 until 144 h post-fertilization (hpf). Chemical analysis showed bioconcentrations of both chemicals, while HBB is readily metabolized to PBB in zebrafish larvae. Embryonic exposure to both chemicals did not cause developmental toxicity, but induced locomotor behavioral anomalies in larvae. Molecular docking results indicated that both chemicals could bind to zebrafish acetylcholinesterase (AChE). Furthermore, HBB and PBB significantly inhibited AChE activities, accompanied by increased contents of acetylcholine and decreased choline in larvae. Downregulation of the genes associated with central nervous system (CNS) development (e.g., mbp, α1-tubulin, gfap, shha) as well as the corresponding proteins (e.g., Mbp, α1-Tubulin) was observed, but gap-43 was upregulated at both gene and protein levels. Together, our results indicate that both HBB and PBB exhibit developmental neurotoxicity by affecting various parameters related to CNS development and indications for future toxicological research and risk assessment of the novel brominated flame retardants.
Show more [+] Less [-]The response of the algae Fucus virsoides (Fucales, Ochrophyta) to Roundup® solution exposure: A metabolomics approach
2019
Felline, S. | Del Coco, L. | Kaleb, S. | Guarnieri, G. | Fraschetti, S. | Terlizzi, A. | Fanizzi, F.P. | Falace, A.
Glyphosate, as a broad-spectrum herbicide, is frequently detected in water and several studies have investigated its effects on several freshwater aquatic organisms. Yet, only few investigations have been performed on marine macroalgae. Here, we studied both the metabolomics responses and the effect on primary production in the endemic brown algae Fucus virsoides exposed to different concentration (0, 0.5, 1.5 and 2.5 mg L⁻¹) of a commercial glyphosate-based herbicide, namely Roundup®. Our results show that Roundup® significantly reduced quantum yield of photosynthesis (Fᵥ/Fₘ) and caused alteration in the metabolomic profiles of exposed thalli compared to controls. Together with the decrease in the aromatic amino acids (phenylalanine and tyrosine), an increase in shikimate content was detected. The branched-amino acids differently varied according to levels of herbicide exposure, as well as observed for the content of choline, formate, glucose, malonate and fumarate. Our results suggest that marine primary producers could be largely affected by the agricultural land use, this asking for further studies addressing the ecosystem-level effects of glyphosate-based herbicides in coastal waters.
Show more [+] Less [-]Enhancing the biodegradation of oil in sandy sediments with choline: A naturally methylated nitrogen compound
2013
Mortazavi, Behzad | Horel, Agota | Anders, Jennifer S. | Mirjafari, Arsalan | Beazley, Melanie J. | Sobecky, Patricia A.
We investigated how additions of choline, a naturally occurring methylated nitrogen-containing compound, accelerated hydrocarbon degradation in sandy sediments contaminated with moderately weathered crude oil (4000 mg kg−1 sediment). Addition of lauroylcholine chloride (LCC) and tricholine citrate (TCC) to oil contaminated sediments resulted in 1.6 times higher hydrocarbon degradation rates compared to treatments without added choline derivatives. However, the degradation rate constant for the oil contaminated sediments amended with LCC was similar to that in contaminated sediments amended with inorganic nitrogen, phosphorus, and glucose. Additions of LLC and TCC to sediments containing extensively weathered oil also resulted in enhanced mineralization rates. Cultivation-free 16S rRNA analysis revealed the presence of an extant microbial community with clones closely related to known hydrocarbon degraders from the Gammaproteobacteria, Alphaproteobacteria, and Firmicutes phyla. The results demonstrate that the addition of minimal amounts of organic compounds to oil contaminated sediments enhances the degradation of hydrocarbons.
Show more [+] Less [-]Estimating the bioaccessibility of flocculants in the presence of sediments in model wastewater
2022
Russell, Derek A. | Hutchinson, R. A. (Robin A.) | Meunier, Louise
The cationic degradable polymer poly(lactic acid) choline iodide ester methacrylate, poly(PLA₄ChMA), can be used to flocculate particles and dewater sediments from tailings ponds and wastewater. A suitable bioaccessibility method is required to characterize the interactions of this novel flocculant in the human gastrointestinal system. To this end, a physiologically based extraction test (PBET) was modified to evaluate the bioaccessibility of flocculants. Bioaccessibility (bioaccessible fraction) is a measure of the solubility of a contaminant in gastrointestinal fluids and that may be available for systemic absorption. The flocculants poly(PLA₄ChMA), SNF C3276, and FLOPAM A3338 were tested at a solid-to-liquid ratio of 1:200 in the absence and presence of kaolin clay, which is used as a model sediment compound. Bioaccessible fractions were characterized by proton nuclear magnetic resonance spectroscopy and estimated by gravimetry. The bioaccessibility of poly(PLA₄ChMA) in gastric and intestinal PBET solutions decreases from 78% and 100%, respectively, in the absence of kaolin to approximately 0% with kaolin, indicating that poly(PLA₄ChMA) remains adsorbed onto the clay surface throughout the PBET, a result confirmed by thermogravimetric analysis. The bioaccessibility of cationic SNF C3276 and anionic FLOPAM A3338 in gastric solution is approximately 76% and 26%, respectively, and is not affected by the presence of kaolin. However, in intestinal solutions, the bioaccessibility of SNF C3276 and FLOPAM A3338 (60–85% in the absence of kaolin) changes to 0% and 100%, respectively, in the presence of kaolin. These results, interpreted in terms of solution pH and surface charge, demonstrate that interactions with kaolin influence the solubility of flocculants and must be considered in the evaluation of bioaccessibility. In future works, such bioaccessibility methods can be applied to assess the human-health safety of using flocculants in wastewater treatments.
Show more [+] Less [-]Toxicity of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) in the marine decapod Litopenaeus vannamei
2019
Su, Yujie | Li, Huifeng | Xie, Jia | Xu, Chang | Dong, Yangfan | Han, Fenglu | Qin, Jian G. | Chen, Liqiao | Li, Erchao
DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is the main component of SeaNine-211, a new antifouling agent that replaces tributyltin to prevent the growth of undesirable organisms on ships. There have been some studies on the toxicity of DCOIT, but the mechanism of DCOIT’s toxicity to crustaceans still requires elucidation. This study examined the chronic toxicity (4 weeks) of 0, 3, 15, and 30 μg/L DCOIT to the Pacific white shrimp (Litopenaeus vannamei) from the aspects of growth and physiological and histological changes in the hepatopancreas and gills. A transcriptomic analysis was performed on the hepatopancreas to reveal the underlying mechanism of DCOIT in shrimp. The exposure to 30 μg/L DCOIT significantly reduced the survival and weight gain of L. vannamei. High Na⁺/K⁺-ATPase activity and melanin deposition were found in the gills after 4 weeks of 15 μg/L or 30 μg/L DCOIT exposure. The highest concentration of DCOIT (30 μg/L) induced changes in hepatopancreatic morphology and metabolism, including high anaerobic respiration and the accumulation of triglycerides. Compared with the exposure to 3 μg/L DCOIT, shrimp exposed to 15 μg/L DCOIT showed more differentially expressed genes (DEGs) than those in the control, and these DEGs were involved in biological processes such as starch and sucrose metabolism and choline metabolism in cancer. The findings of this study indicate that L. vannamei is sensitive to the antifouling agent DCOIT and that DCOIT can induce altered gene expression at a concentration of 15 μg/L and can interfere with shrimp metabolism, growth and survival at 30 μg/L.
Show more [+] Less [-]Transcriptomic and metabolomic associations with exposures to air pollutants among young adults with childhood asthma history
2022
Liao, Jiawen | Gheissari, Roya | Thomas, Duncan C. | Gilliland, Frank D. | Lurmann, Fred | Islam, Khandaker Talat | Chen, Zhanghua
Ambient air pollutants are well-known risk factors for childhood asthma and asthma exacerbation. It is unknown whether different air pollutants individually or jointly affect pathophysiological mechanisms of asthma. In this study, we aim to integrate transcriptome and untargeted metabolome to identify dysregulated genetic and metabolic pathways that are associated with exposures to a mixture of ambient and traffic-related air pollutants among adults with asthma history. In this cross-sectional study, 102 young adults with childhood asthma history were enrolled from southern California in 2012. Whole blood transcriptome was measured with 20,869 expression signatures, and serum untargeted metabolomics including 937 metabolites were analyzed by Metabolon, Inc. Participants’ exposures to regional air pollutants (NO₂, O₃, PM₁₀, PM₂.₅) and near-roadway air pollutants averaged at one month and one year before study visit were estimated based on residential addresses. xMWAS network analysis and joint-pathway analysis were performed to identify subnetworks and genetic and metabolic pathways that were associated with exposure to air pollutants adjusted for socio-characteristic covariates. Network analysis found that exposures to air pollutants mixture were connected to 357 gene markers and 92 metabolites. One-year and one-month averaged PM₂.₅ and NO₂ were associated with several amino acids related to serine, glycine, and beta-alanine metabolism. Lower serum levels of carnosine and aspartate, which are involved in the beta-alanine metabolic pathway, as well as choline were also associated with worse asthma control (p < 0.05). One-year and one-month averaged PM₁₀ and one-month averaged O₃ were associated with higher gene expression levels of HSPA5, LGMN, CTSL and HLA-DPB1, which are involved in antigen processing and presentation. These results indicate that exposures to various air pollutants are associated with altered genetic and metabolic pathways that affect anti-oxidative capacity and immune response and can potentially contribute to asthma-related pathophysiology.
Show more [+] Less [-]Ionic liquid-biosurfactant blends as effective dispersants for oil spills: Effect of carbon chain length and degree of saturation
2021
Hassan Shah, Mansoor Ul | Bhaskar Reddy, Ambavaram Vijaya | Suzana Yusup, | Goto, Masahiro | Moniruzzaman, Muhammad
The well-known toxicity of conventional chemical oil spill dispersants demands the development of alternative and environmentally friendly dispersant formulations. Therefore, in the present study we have developed a pair of less toxic and green dispersants by combining lactonic sophorolipid (LS) biosurfactant individually with choline myristate and choline oleate ionic liquid surfactants. The aggregation behavior of resulted surfactant blends and their dispersion effectiveness was investigated using the baffled flask test. The introduction of long hydrophobic alkyl chain with unsaturation (attached to choline cation) provided synergistic interactions between the binary surfactant mixtures. The maximum dispersion effectiveness was found to be 78.23% for 80:20 (w/w) lactonic sophorolipid-choline myristate blends, and 81.15% for 70:30 (w/w) lactonic sophorolipid-choline oleate blends at the dispersant-to-oil ratio of 1:25 (v/v). The high dispersion effectiveness of lactonic sophorolipid-choline oleate between two developed blends is attributed to the stronger synergistic interactions between surfactants and slower desorption rate of blend from oil-water interface. The distribution of dispersed oil droplets at several DOR were evaluated and it was observed that oil droplets become smaller with increasing DOR. In addition, the acute toxicity analysis of developed formulations against zebra fish (Danio rerio) confirmed their non-toxic behavior with LC₅₀ values higher than 400 ppm after 96 h. Overall, the proposed new blends/formulations could effectively substitute the toxic and unsafe chemical dispersants.
Show more [+] Less [-]Targeted metabolomics reveals that 2,3,7,8-tetrachlorodibenzofuran exposure induces hepatic steatosis in male mice
2020
Yuan, Peihong | Dong, Manyuan | Lei, Hehua | Xu, Guangyong | Chen, Gui | Song, Yuchen | Ma, Jianfeng | Cheng, Liming | Zhang, Limin
Environmental exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF), one of typical persistent organic pollutants (POPs) produced from municipal waste combustion, exerts toxic effects on human healthy. In the current study, we mainly used targeted metabolomics combined with untargeted ¹H NMR-based metabolomics to investigate the effects of TCDF exposure on lipid homeostasis in mice. We found that TCDF exposure induced hepatic lipogenesis, the early-stage of non-alcoholic fatty liver disease, manifested by excessive lipids including triglycerides, fatty acids and lipotoxic ceramides accumulated in the liver together with elevated serum very low-density lipoprotein by activating the aryl hydrocarbon receptor (AHR) and its target genes such as Cyp1a1 and Cd36. We also found that TCDF exposure induced alteration of phospholipids and choline metabolites and endoplasmic reticulum (ER) markers in the liver of mice, indicating that disruption of host cell membrane structural integrity and ER stress leading to hepatic steatosis. In addition, complementary information was also obtained from histopathologic assessments and biological assays, strongly supporting toxic effects of TCDF. These results provide new evidence of TCDF toxicity associated with fatty liver disease and further our understanding of health effects of environmental pollutants exposure.
Show more [+] Less [-]Untargeted NMR-based metabolomics for field-scale monitoring: Temporal reproducibility and biomarker discovery in mosquitofish (Gambusia holbrooki) from a metal(loid)-contaminated wetland
2018
Melvin, Steven D. | Lanctôt, Chantal M. | Doriean, Nicholas J.C. | Carroll, Anthony R. | Bennett, William W.
There is considerable interest in applying omics techniques, which have proven extremely valuable for laboratory-based toxicology studies, towards field-scale ecotoxicology and environmental monitoring. Concerns that confounding factors in natural ecosystems may exacerbate variability in omics datasets must be addressed to validate the transition from laboratory to field. This study explores how temporal variability related to seasonal and climatic trends influence qualitative and quantitative metabolomics outcomes, in fish from reference and metal(loid)-polluted wetlands in Australia. Female mosquitofish (Gambusia holbrooki) were sampled on two separate occasions, from a rehabilitated tailings wetland at the site of historic antimony (Sb) processing and a reference wetland with comparable water quality. The first sampling coincided with greater monthly rainfall and colder water temperature, whereas the second sampling was drier and water was warmer. Despite temporal changes and associated differences in metal(loid) concentrations, site differences in metabolite profiles were qualitatively very similar between sampling events. However, quantitative differences were observed, with a greater number of significantly altered metabolites identified during the second sampling event, which coincided with greater metal(loid) concentrations in both water and fish. The majority of identified metabolites were elevated in fish from the contaminated wetland, but with notable decreases in several metabolites that are known to play a role in various aspects of metal(loid) binding, detoxification and excretion. Specifically, decreased aspartate, histidine, myo-inositol, taurine and choline were observed in fish from the contaminated wetland, and may therefore represent a metabolite suite that is broadly indicative of metal toxicity. Quantitative differences between sampling events are suggestive of a dose-response relationship observable at the cellular level which, if harnessed, may be useful for assigning levels of concern based on the degree of change in a multi-parameter set of metabolite biomarkers.
Show more [+] Less [-]