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.

Insufficient evidence exists regarding the visible physiological toxic endpoints of MPs exposures on zebrafish larvae due to their small sizes. Herein, the impacts of micro-polystyrene particles (μ-PS) and 100 nm polystyrene particles (n-PS) on the toxicity of cadmium (Cd) through altering neutrophil expressions were identified and quantified in the transgenic zebrafish (Danio rerio) larvae Tg(lyz:DsRed2), and the effects were size-dependent. When exposed together with μ-PS, the amount of neutrophils in Cd treated zebrafish larvae decreased by 25.56% through reducing Cd content in the larvae. By contrast, although n-PS exposure caused lower Cd content in the larvae, the expression of neutrophils under their combined exposure remained high. The mechanism of immune toxicity was analyzed based on the results of metabonomics. n-PS induced high oxidative stress in the larvae, which promoted taurine metabolism and unsaturated fatty biosynthesis in n-PS + Cd treatment. This observation was accordance with the significant inhibition of the activities of superoxide dismutase and catalase enzymes detected in their combined treatment. Moreover, n-PS promoted the metabolic pathways of catabolic processes, amino acid metabolism, purine metabolism, and steroid hormone biosynthesis in Cd treated zebrafish larvae. Nanoplasctis widely coexist with other pollutants in the environment at relatively low concentrations. We conclude that more bio-markers of immune impact should be explored to identify their toxicological mechanisms and mitigate the effects on the environment.

Mercury (Hg) is recognized as a dangerous contaminant due to its bioaccumulation and biomagnification within trophic levels, leading to serious health risks to aquatic biota. Therefore, there is an urgent need to unravel the mechanisms underlying the toxicity of Hg. To this aim, a metabolomics approach based on protonic nuclear magnetic resonance (1H NMR), coupled with chemometrics, was performed on the gills of wild golden grey mullets L. aurata living in an Hg-polluted area in Ria de Aveiro (Portugal). Gills were selected as target organ due to their direct and continuous interaction with the surrounding environment. As a consequence of accumulated inorganic Hg and methylmercury, severe changes in the gill metabolome were observed, indicating a compromised health status of mullets. Numerous metabolites, i.e. amino acids, osmolytes, carbohydrates, and nucleotides, were identified as potential biomarkers of Hg toxicity in fish gills. Specifically, decrease of taurine and glycerophosphocholine, along with increased creatine level, suggested Hg interference with the ion-osmoregulatory processes. The rise of lactate indicated anaerobic metabolism enhancement. Moreover, the increased levels of amino acids suggested the occurrence of protein catabolism, further supported by the augmented alanine, involved in nitrogenous waste excretion. Increased level of isobutyrate, a marker of anoxia, was suggestive of onset of hypoxic stress at the Hg contaminated site. Moreover, the concomitant reduction in glycerophosphocholine and phosphocholine reflected the occurrence of membrane repair processes. Finally, perturbation in antioxidant defence system was revealed by the depletion in glutathione and its constituent amino acids. All these data were also compared to the differential Hg-induced metabolic responses previously observed in liver of the same mullets (Brandão et al., 2015). Overall, the environmental metabolomics approach demonstrated its effectiveness in the evaluation of Hg toxicity mechanisms in wild fish under realistic environmental conditions, uncovering tissue-specificities regarding Hg toxic effects namely in gills and liver.

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.

Coastal hypoxia affects the survival, behavior, and reproduction of individual local marine organisms, and the abundance, biomass, and biodiversity of coastal ecosystems. In this study, we investigated the chronic effects of hypoxia on the metabolomics in the gills of Ruditapes (R.) philippinarum. The results indicated significant alterations in the metabolite profiles in the gills of the hypoxia-treated clams, in comparison with those maintained under normoxia. The levels of betaine, taurine, glycine, isoleucine, and alanine were significantly reduced, suggesting a disturbance of osmotic balance associated with hypoxia. Meanwhile, metabolites involved in energy metabolism, such as alanine and succinate, were also affected. Dramatic histopathological changes were observed in the gills and hepatopancreases of R. philippinarum grown in hypoxic waters, demonstrating tissue damages apparently caused by long-term exposure to hypoxia. Our findings suggest that hypoxia significantly affects the physiology of R. philippinarum, even at a sub-lethal level, and impedes health of the clams.

Triazophos, as a lipophilic organophosphate pesticide, displays higher bioaccumulation in the gonads of shellfish. To study the reproductive toxicity of triazophos, we applied metabolomics to characterize the gender-specific metabolic responses in mussel Perna viridis exposed to triazophos. Metabolites were differently altered by triazophos in ovaries of mussel at different concentrations and time intervals, while basically similar metabolic response patterns were observed in male mussels at the two tested concentrations after exposure for 24 and 48h. The significant changes of metabolites in ovaries of mussel exhibited the disturbances in energy metabolism and osmotic regulation, while in male samples triazophos only affected the energy metabolism. Moreover, glycine, sn-glycero-3-phosphocholine, ethanol, aspartate, etc. exhibited consistent variation tendency in both male and female individuals. While the changes of homarine, betaine, taurine, hypotaurine, malonate, β-alanine, succinate, and choline showed obviously gender-specific responses. Overall, this study confirmed the gender-specific responses in gonad of P. viridis to triazophos exposure.

The 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is the predominant congener of polybrominated diphenyl ethers, and it is also a persistent organic pollutant that with a higher detection rate in samples from environment and animals. To date, there have been few studies of the effects of BDE-47 on locomotion in sea cucumbers. In this study, we investigated the influence of different concentrations of BDE-47 (low: 0.1 μg/L; moderate: 1.0 μg/L; high: 10.0 μg/L) on locomotion of Apostichopus japonicus and evaluated changes in their muscle physiology using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The behavioural studies showed that the average and maximum velocity of movement decreased significantly in both the moderate and high BDE-47 groups after 1 day of exposure. In addition, levels of 55 metabolites were identified and characterized in the longitudinal muscle of A. japonicus exposed to BDE-47. The alteration of taurine and norepinephrine levels indicated that BDE-47 had drastic physiological effects on the longitudinal muscle of A. japonicus.

Bisphenol A (BPA) received heightened attention in the recent years due to humans continuously being exposed to it. This study explores the effect of taurine or curcumin on subacute BPA treatment-induced nephrotoxicity in rats (Rattus norvegicus). Forty-two adult albino male rats were exposed to BPA (130 mg/kg daily) for 28 days by gastric gavage. BPA led to lipid peroxidation, inhibiting antioxidant enzyme activities like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST). BPA exposure also induced histopathological changes like tubular and glomerular degeneration, vascular congestion, and interstitial cell infiltration in kidney tissue. Cotreatment with taurine (100 mg/kg daily) or curcumin (100 mg/kg daily) alleviated the lipid peroxidation level and antioxidant enzyme activities and histological alterations brought about by BPA. In this study, curcumin and taurine application provided protection against renal toxicity caused by BPA but did not prevent toxic effect completely.

Analysis of brown bullhead (Ameiurus nebulosus) bile by ultra performance liquid chromatography high-resolution mass spectrometry (UPLC/HRMS) revealed a series of bile acids similar to those found in humans. Accordingly, we chose this fish as a model organism to examine the metabolism of obeticholic acid, a bile acid used to treat a number of human liver diseases and the one that has the potential to occur as an environmental contaminant. The taurine and glycine conjugates of obeticholic acid and keto-obeticholic acid were identified, as well as the D-cysteinolic acid conjugate of obeticholic acid, likely a metabolite specific to fish. In addition, metabolites of obeticholic acid (sulphate and glucuronide) and several hydroxy-obeticholic acid derivatives were found, representing typical pathways of primary and secondary steroid metabolism. Brown bullhead exposed to obeticholic acid at a dose of 100 mg/kg gave no overt signs of distress or toxicity.

Chromium is used in daily life and has a wide range of functions. It plays an important role in protein synthesis and carbohydrate and lipid metabolism. Chromium is found in trivalent Cr(III) and hexavalent Cr(VI) form; Cr(III) is relatively stable and intimately participates with many phenomena of metabolisms. Whereas, Cr(VI) is toxic, which results in growth inhibition and leading to changes in components of antioxidant systems as well as secondary metabolites. However, the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is still unclear. For this purpose, 40 chickens were randomly assigned into two groups: the normal group (feeding the basic diet and clear water), the chromium group (16%LD₅₀, 74.24 mg/kg/day K₂Cr₂O₇). The samples were subjected to pathological examination and UHPLC-QE-MS non-target metabolomics method for metabolomics analysis of broiler liver using principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA). The central venous cells of the broiler liver in the chromium poisoning group showed turbidity and flaky necrosis, nuclear condensation, nuclear rupture, and even nuclear dissolution. The differential metabolite analysis between the chromium poisoning and the control group showed that 32 differential metabolites were upregulated and 15 were downregulated in positive ion mode. Whereas,17 differential metabolites were downregulated, and 35 were downregulated in negative ion mode (P ≤ 0.05). The potential marker substances are oleic acidamide, farnesylacetone, betaine, taurine, choline, and galactinol. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the lipid metabolism, carbohydrate metabolism, nucleotide metabolism, amino acid metabolism, energy metabolism, membrane transport, digestive system, and nervous system were the most important metabolic pathways in the liver. This study provides a theoretical basis for the future understanding of the pathogenesis of chromium poisoning and a new insight of the subsequent molecular mechanism of chromium hepatotoxicity.