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Subchronic exposure to concentrated ambient PM2.5 perturbs gut and lung microbiota as well as metabolic profiles in mice
2021
Ran, Zihan | An, Yanpeng | Zhou, Ji | Yang, Jingmin | Zhang, Youyi | Yang, Jingcheng | Wang, Lei | Li, Xin | Lu, Daru | Zhong, Jiang | Song, Huaidong | Qin, Xingjun | Li, Rui
Exposure to ambient fine particular matter (PM2.5) are linked to an increased risk of metabolic disorders, leading to enhanced rate of many diseases, such as inflammatory bowel disease (IBD), cardiovascular diseases, and pulmonary diseases; nevertheless, the underlying mechanisms remain poorly understood. In this study, BALB/c mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CPM) for 2 months using a versatile aerosol concentration enrichment system(VACES). We found subchronic CPM exposure caused significant lung and intestinal damage, as well as systemic inflammatory reactions. In addition, serum and BALFs (bronchoalveolar lavage fluids) metabolites involved in many metabolic pathways in the CPM exposed mice were markedly disrupted upon PM2.5 exposure. Five metabolites (glutamate, glutamine, formate, pyruvate and lactate) with excellent discriminatory power (AUC = 1, p < 0.001) were identified to predict PM2.5 exposure related toxicities. Furthermore, subchronic exposure to CPM not only significantly decreased the richness and composition of the gut microbiota, but also the lung microbiota. Strong associations were found between several gut and lung bacterial flora changes and systemic metabolic abnormalities. Our study showed exposure to ambient PM2.5 not only caused dysbiosis in the gut and lung, but also significant systemic and local metabolic alterations. Alterations in gut and lung microbiota were strongly correlated with metabolic abnormalities. Our study suggests potential roles of gut and lung microbiota in PM2.5 caused metabolic disorders.
Show more [+] Less [-]NMR-based metabolic toxicity of low-level Hg exposure to earthworms
2018
Tang, Ronggui | Ding, Changfeng | Dang, Fei | Ma, Yibing | Wang, Junsong | Zhang, Taolin | Wang, Xingxiang
Mercury is a globally distributed toxicant to aquatic animals and mammals. However, the potential risks of environmental relevant mercury in terrestrial systems remain largely unclear. The metabolic profiles of the earthworm Eisenia fetida after exposure to soil contaminated with mercury at 0.77 ± 0.09 mg/kg for 2 weeks were investigated using a two-dimensional nuclear magnetic resonance-based (¹H-¹³C NMR) metabolomics approach. The results revealed that traditional endpoints (e.g., mortality and weight loss) did not differ significantly after exposure. Although histological examination showed sub-lethal toxicity in the intestine as a result of soil ingestion, the underlying mechanisms were unclear. Metabolite profiles revealed significant decreases in glutamine and 2-hexyl-5-ethyl-3-furansulfonate in the exposed group and remarkable increases in glycine, alanine, glutamate, scyllo-inositol, t-methylhistidine and myo-inositol. More importantly, metabolic network analysis revealed that low mercury in the soil disrupted osmoregulation, amino acid and energy metabolisms in earthworms. A metabolic net link and schematic diagram of mercury-induced responses were proposed to predict earthworm responses after exposure to mercury at environmental relevant concentrations. These results improved the current understanding of the potential toxicity of low mercury in terrestrial systems.
Show more [+] Less [-]Integration of environmental metabolomics and physiological approach for evaluation of saline pollution to rice plant
2021
Ma, Nyuk Ling | Lam, Su Datt | Che Lah, Wan Afifudeen | Aḥmad, ʻAzīz | Rinklebe, Jörg | Sonne, Christian | Peng, Wanxi
Salinisation of soil is associated with urban pollution, industrial development and rising sea level. Understanding how high salinity is managed at the plant cellular level is vital to increase sustainable farming output. Previous studies focus on plant stress responses under salinity tolerance. Yet, there is limited knowledge about the mechanisms involved from stress state until the recovery state; our research aims to close this gap. By using the most tolerance genotype (SS1-14) and the most susceptible genotype (SS2-18), comparative physiological, metabolome and post-harvest assessments were performed to identify the underlying mechanisms for salinity stress recovery in plant cells. The up-regulation of glutamine, asparagine and malonic acid were found in recovered-tolerant genotype, suggesting a role in the regulation of panicle branching and spikelet formation for survival. Rice could survive up to 150 mM NaCl (∼15 ds/m) with declined of production rate 5–20% ranged from tolerance to susceptible genotype. This show that rice farming may still be viable on the high saline affected area with the right selection of salt-tolerant species, including glycophytes. The salt recovery biomarkers identified in this study and the adaption underlined could be empowered to address salinity problem in rice field.
Show more [+] Less [-]The associations of nitrated polycyclic aromatic hydrocarbon exposures with plasma glucose and amino acids
2021
He, Linchen | Hu, Xinyan | Day, Drew B. | Yan, Meilin | Teng, Yanbo | Liu, Xing (Lucy) | Yan, Erik | Xiang, Jianbang | Qiu, Xinghua | Mo, Jinhan | Zhang, Yinping | Zhang, Junfeng (Jim) | Gong, Jicheng
Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) have been widely studied for their mutagenic and carcinogenic effects. This study aims to investigate whether exposure to nitro-PAHs is associated with biomarkers of carbohydrate metabolism, an underlying risk factor for metabolic disorder. Early morning urine and blood samples were longitudinally collected two times with a four-week interval from 43 healthy adults. Five urinary amino-PAHs (1-aminonaphthalene, 2-aminonaphthalene, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene) were measured as biomarkers of nitro-PAH exposures. We measured plasma concentrations of glucose and six amino acids that can regulate insulin secretion, including aspartate (Asp), glutamate (Glu), glutamine (Gln), alanine (Ala), Arginine (Arg), and ornithine (Orn). We found that increasing concentrations of 9-aminophenanthrene were significantly associated with increasing glucose levels and with decreasing Asp, Glu, Ala, and Orn levels. We estimated that 26.4 %–43.8 % of the 9-aminophenanthrene-associated increase in glucose level was mediated by Asp, Glu, and Orn. These results suggest that exposure to certain nitro-PAHs affects glucose homeostasis, partly resulting from the depletion of insulin-stimulating amino acids (Asp, Glu, and Orn).
Show more [+] Less [-]Effect of organochlorine pesticides exposure on the maize root metabolome assessed using high-resolution magic-angle spinning 1H NMR spectroscopy
2016
1H-HRMAS NMR-based metabolomics was used to better understand the toxic effects on maize root tips of organochlorine pesticides (OCPs), namely lindane (γHCH) and chlordecone (CLD). Maize seedlings were exposed to 2.5 μM γHCH (mimicking basic environmental contaminations) for 7 days and compared to 2.5 μM CLD and 25 μM γHCH for 7 days (mimicking hot spot contaminations). The 1H-HRMAS NMR-based metabolomic profiles provided details of the changes in carbohydrates, amino acids, tricarboxylic acid (TCA) cycle intermediates and fatty acids with a significant separation between the control and OCP-exposed root tips. First of all, alterations in the balance between glycolysis/gluconeogenesis were observed with sucrose depletion and with dose-dependent fluctuations in glucose content. Secondly, observations indicated that OCPs might inactivate the TCA cycle, with sizeable succinate and fumarate depletion. Thirdly, disturbances in the amino acid composition (GABA, glutamine/glutamate, asparagine, isoleucine) reflected a new distribution of internal nitrogen compounds under OCP stress. Finally, OCP exposure caused an increase in fatty acid content, concomitant with a marked rise in oxidized fatty acids which could indicate failures in cell integrity and vitality. Moreover, the accumulation of asparagine and oxidized fatty acids with the induction of LOX3 transcription levels under OCP exposure highlighted an induction of protein and lipid catabolism. The overall data indicated that the effect of OCPs on primary metabolism could have broader physiological consequences on root development. Therefore, 1H-HRMAS NMR metabolomics is a sensitive tool for understanding molecular disturbances under OCP exposure and can be used to perform a rapid assessment of phytotoxicity.
Show more [+] Less [-]1H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil
2010
1H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50-1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-β-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised ∼65-97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils.
Show more [+] Less [-]Polystyrene microplastics up-regulates liver glutamine and glutamate synthesis and promotes autophagy-dependent ferroptosis and apoptosis in the cerebellum through the liver-brain axis
2022
Yin, Kai | Wang, Dongxu | Zhao, Hongjing | Wang, Yu | Zhang, Yue | Liu, Yachen | Li, Baoying | Xing, Mingwei
Microplastics (MPs), which are emerging environmental pollutants, remain uncertainties in their toxic mechanism. MPs have been linked to severe liver metabolic disorders and neurotoxicity, but it is still unknown whether the abnormal metabolites induced by MPs can affect brain tissue through the liver-brain axis. Exposed to MPs of chickens results in liver metabolic disorders and increased glutamine and glutamate synthesis. The relative expression of glutamine in the C group was −0.862, the L-PS group was 0.271, and the H-PS group was 0.592. The expression of tight junction proteins in the blood-brain barrier (BBB) was reduced by PS-MPs. Occludin protein expression decreased by 35.8%–41.2%. Claudin 3 decreased by 19.6%–42.3%, and ZO-1 decreased by 28.3%–44.6%. Excessive glutamine and glutamate cooperated with PS-MPs to inhibit the Nrf2-Keap1-HO-1/NQO1 signaling pathway and triggered autophagy-dependent ferroptosis and apoptosis. GPX protein expression decreased by 30.9%–38%. LC3II/LC3I increased by 54%, and Caspase 3 increased by 45%. Eventually, the number of Purkinje cells was reduced, causing neurological dysfunction. In conclusion, this study provides new insights for revealing the mechanism of nervous system damaged caused by PS-MPs exposed in chickens.
Show more [+] Less [-]Simultaneous removal of acid green 25 and mercury ions from aqueous solutions using glutamine modified chitosan magnetic composite microspheres
2016
Tao, Xue | Li, Kun | Yan, Han | Yang, Hu | Li, Aimin
In this current work, the magnetic composite microsphere containing glutamine modified chitosan and silica coated Fe3O4 nanoparticles (CS-Gln-MCM) has been successfully prepared and extensively characterized, which is a kind of biodegradable materials. CS-Gln-MCM shows enhanced removal efficiency for both acid green 25 (AG25), an amphoteric dye, and mercury ions (Hg²⁺) from water in the respective while measured pH range compared with chitosan magnetic composite microsphere (CS-MCM) without modification. It is due to the fact that the grafted amino acid provides a variety of additional adsorption active sites and diverse adsorption mechanisms are involved. In AG25 and Hg²⁺ aqueous mixture, the modified adsorbents bear preferential adsorption for AG25 over Hg²⁺ in strong acidic solutions ascribed to multiple interactions between AG25 and CS-Gln-MCM, such as hydrogen bonding and electrostatic interactions. While, in weak acidic conditions, an efficient simultaneous removal is observed for different adsorption effects involved in aforementioned two pollutants. Besides, CS-Gln-MCM illuminates not only short equilibrium time for adsorption of each pollutant less than 20.0 min but also rapid magnetic separation from water and efficient regeneration after saturated adsorption. Therefore, CS-Gln-MCM bears great application potentials in water treatment.
Show more [+] Less [-]Metabolome responses of the sea cucumber Apostichopus japonicus to multiple environmental stresses: Heat and hypoxia
2019
Huo, Da | Sun, Lina | Zhang, Libin | Ru, Xiaoshang | Liu, Shilin | Yang, Hongsheng
Economically important marine organisms face severe environmental challenges, such as high temperature and low dissolved oxygen, from global climate change. Adverse environmental factors impact the survival and growth of economically important marine organisms, thereby negatively influencing the aquaculture industry. However, little is known about the responses of sea cucumbers to combined environmental co-stressors till now. In this study, ultra-performance liquid chromatography (UPLC) was utilized to obtain metabolic profiles of sea cucumbers. Changes in the concentrations of 84, 68, and 417 metabolites related to the responses of sea cucumbers to heat (26 °C), hypoxia (2 mg/L) and the combined stress, respectively, were observed and analyzed. Representative biomarkers were discussed in detail, including deltaline, fusarin C, halichondrin B and rapanone. The concentration of metabolites involved in the regulation of energy metabolism, including amino acid, carbohydrate and lipid metabolism were significantly changed, and the tricarboxylic acid (TCA)-cycle was significantly altered under heat plus hypoxia. We interpreted these changes partly as an adaptation mechanism in response to environmental stress. Based on the decreased accumulation of glutamine, we hypothesized that heat stress is the main factor that interferes with the process of glutamic acid-glutamine metabolism. The present study showed that combined environmental stressors have a more extensive impact on the metabolites of the respiratory tree in sea cucumbers than single stress. These results would facilitate further development of the sea cucumber as an echinoderm model to study mechanisms of response to adverse environments, as well as to help advance knowledge of the adaptation of marine organisms to global climate change.
Show more [+] Less [-]Metabolic responses to metal pollution in shrimp Crangon affinis from the sites along the Laizhou Bay in the Bohai Sea
2016
Xu, Lanlan | Ji, Chenglong | Zhao, Jianmin | Wu, Huifeng
Marine environment in the Laizhou Bay is potentially contaminated by metals from industrial discharges. In this study, metal concentrations in shrimps Crangon affinis indicated that two typical sites (S6283 and S5283) close to Longkou and Zhaoyuan cities along the Laizhou Bay have been contaminated by metals, including Cd, As, Cu, Ni, Co, and Mn. In particular, Cd and As were the main metal contaminants in S6283. In S5283, however, Cu was the most important metal contaminant. The metabolic responses in the shrimps indicated that the metal pollution in S6283 and S5283 induced disturbances in osmotic regulation and energy metabolism and reduced anaerobiosis, lipid metabolism, and muscle movement. However, alteration in the levels of dimethylglycine, dimethylamine, arginine, betaine, and glutamine indicated that the metal pollution in S5283 induced osmotic stress through different pathways compared to that in S6283. In addition, dimethylamine might be the biomarker of Cu in shrimp C. affinis.
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