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Metabolites
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Environmental Toxicology and Metabolism
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Environmental Toxicology and Metabolism

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Environmental Metabolomics".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 13040

Special Issue Editor

Prof. Dr. Yu Sun

E-Mail Website
Guest Editor
College of life sciences, South China Agricultural University, Guangzhou, China
Interests: Indoor microbiome and metabolome; human gut microbiome; asthma and rhinitis; mycotoxin

Special Issue Information

Dear Colleagues,

We are pleased to announce a special issue of the journal "Metabolites" dedicated to the latest research in the field of environmental toxicology and metabolism.

The special issue will focus on the latest advances in understanding the mechanisms of toxicity and metabolism of environmental pollutants, as well as the impacts of these pollutants on human health and the environment. Topics of interest include, but are not limited to:

  • Mechanisms of toxicity and metabolism of environmental pollutants
  • Biomarkers of exposure and effect
  • Environmental epidemiology and risk assessment
  • Enivronmental microbiome and metabolome
  • Ecotoxicology and wildlife toxicology
  • Metabolomics and systems biology approaches to understanding toxicity
  • Advances in analytical chemistry and bioanalytical techniques for environmental toxicology

Development of new tools and techniques for environmental toxicology and metabolism research

We welcome submissions of original research articles, reviews, and perspectives on these topics. All submissions will undergo a rigorous peer-review process.

We look forward to receiving your contributions and to publishing a high-quality special issue that will be of interest to a broad audience of researchers, practitioners, and policymakers working in the field of environmental toxicology and metabolism.

If you have any questions or would like to discuss a potential submission, please do not hesitate to contact the guest editors or the editorial office of "Metabolites".

Prof. Dr. Yu Sun
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • environmental pollutants
  • ecotoxicity
  • microbiome
  • metabolomics
  • mycotoxin
  • environmental exposure
  • risk assessment
  • toxicokinetics

Published Papers (9 papers)

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Research

13 pages, 2204 KiB  
Article
Effects of Astragaloside IV on Hearing, Inflammatory Factors, and Intestinal Flora in Mice Exposed to Noise
by Junyi Li, Jian Yang, Yun Xia, Junyi Wang and Yuan Xia
Metabolites 2024, 14(2), 122; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo14020122 - 11 Feb 2024
Cited by 1 | Viewed by 1159
Abstract
Long-term exposure to noise can cause irreversible hearing loss. Considering that there is no effective drug treatment, it is important to seek preventive treatment for noise-induced hearing loss (NIHL). Although astragaloside IV (AS-IV) protects against NIHL by reducing serum inflammatory factors, there is [...] Read more.
Long-term exposure to noise can cause irreversible hearing loss. Considering that there is no effective drug treatment, it is important to seek preventive treatment for noise-induced hearing loss (NIHL). Although astragaloside IV (AS-IV) protects against NIHL by reducing serum inflammatory factors, there is scarce information on the regulation of inflammatory factors by AS-IV to prevent NIHL. We investigated the hearing thresholds and relationship between the serum levels of inflammatory cytokines and intestinal microbiota of c57bl/6j mice exposed to noise (103 dB SPL 4 h·d−1) for 7 days, treated with or without AS-IV. Our results revealed a lower hearing threshold and lower serum levels of TNF-α, TNF-γ, IL-6, IL-1β, and IFN-γ in the mice treated with AS-IV. Additionally, AS-IV increased the abundance levels of the phylum Firmicutes, class Bacillus, order Lactobacillus, and family Lactobacillus (p < 0.05), and decreased those of the phylum Bacteroidetes and order Bacteroidales (p < 0.05). Lactobacillus and Bacilli negatively correlated with TNF-α, TNF-γ, and IL-1β; Erysipelotrichaceae negatively correlated with INF-γ; and Clostridiales positively correlated with IL-1β. In conclusion, AS-IV reduces the elevation of hearing thresholds in mice, preventing hearing loss in mice exposed to noise, and under the intervention of AS-IV, changes in the levels of inflammatory factors correlate with intestinal flora. We suggest that AS-IV improves intestinal flora and reduces inflammation levels in c57bl/6j mice exposed to noise. Full article
(This article belongs to the Special Issue Environmental Toxicology and Metabolism)
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19 pages, 4048 KiB  
Article
The Role of Indoor Microbiome and Metabolites in Shaping Children’s Nasal and Oral Microbiota: A Pilot Multi-Omic Analysis
by Mei Zhang, Hao Tang, Yiwen Yuan, Zheyuan Ou, Zhuoru Chen, Yanyi Xu, Xi Fu, Zhuohui Zhao and Yu Sun
Metabolites 2023, 13(10), 1040; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo13101040 - 27 Sep 2023
Cited by 2 | Viewed by 1590
Abstract
Maintaining a diverse and well-balanced nasal and oral microbiota is vital for human health. However, the impact of indoor microbiome and metabolites on nasal and oral microbiota remains largely unknown. Fifty-six children in Shanghai were surveyed to complete a questionnaire about their personal [...] Read more.
Maintaining a diverse and well-balanced nasal and oral microbiota is vital for human health. However, the impact of indoor microbiome and metabolites on nasal and oral microbiota remains largely unknown. Fifty-six children in Shanghai were surveyed to complete a questionnaire about their personal and environmental characteristics. The indoor microbiome and metabolites from vacuumed indoor dust were profiled via shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC–MS). The nasal and oral microbiota in children was characterized using full-length 16S rRNA sequencing from PacBio. Associations between personal/environmental characteristics and the nasal/oral microbiota were calculated using PERMANOVA and regression analyses. We identified 6247, 431, and 342 microbial species in the indoor dust, nasal, and oral cavities, respectively. The overall nasal and oral microbial composition showed significant associations with environmental tobacco smoke (ETS) exposure during pregnancy and early childhood (p = 0.005 and 0.03, respectively), and the abundance of total indoor flavonoids and two mycotoxins (deoxynivalenol and nivalenol) (p = 0.01, 0.02, and 0.03, respectively). Notably, the abundance of several flavonoids, such as baicalein, eupatilin, isoliquiritigenin, tangeritin, and hesperidin, showed positive correlations with alpha diversity and the abundance of protective microbial taxa in nasal and oral cavities (p < 0.02), suggesting their potential beneficial roles in promoting nasal/oral health. Conversely, high carbohydrate/fat food intake and ETS exposure diminished protective microorganisms while augmenting risky microorganisms in the nasal/oral cavities. Further, potential microbial transfer was observed from the indoor environment to the childhood oral cavity (Moraxella catarrhalis, Streptococcus mitis, and Streptococcus salivarius), which could potentially increase virulence factors related to adherence and immune modulation and vancomycin resistance genes in children. This is the first study to reveal the association between the indoor microbiome/metabolites and nasal/oral microbiota using multi-omic approaches. These findings reveal potential protective and risk factors related to the indoor microbial environment. Full article
(This article belongs to the Special Issue Environmental Toxicology and Metabolism)
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16 pages, 1698 KiB  
Article
Metabolic Alteration of MCF-7 Cells upon Indirect Exposure to E. coli Secretome: A Model of Studying the Microbiota Effect on Human Breast Tissue
by Reem H. AlMalki, Malak A. Jaber, Mysoon M. Al-Ansari, Khalid M. Sumaily, Monther Al-Alwan, Essa M. Sabi, Abeer K. Malkawi and Anas M. Abdel Rahman
Metabolites 2023, 13(8), 938; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo13080938 - 11 Aug 2023
Viewed by 1260
Abstract
According to studies, the microbiome may contribute to the emergence and spread of breast cancer. E. coli is one of the Enterobacteriaceae family recently found to be present as part of the breast tissue microbiota. In this study, we focused on the effect [...] Read more.
According to studies, the microbiome may contribute to the emergence and spread of breast cancer. E. coli is one of the Enterobacteriaceae family recently found to be present as part of the breast tissue microbiota. In this study, we focused on the effect of E. coli secretome free of cells on MCF-7 metabolism. Liquid chromatography–mass spectrometry (LC-MS) metabolomics was used to study the E. coli secretome and its role in MCF-7 intra- and extracellular metabolites. A comparison was made between secretome-exposed cells and unexposed controls. Our analysis revealed significant alterations in 31 intracellular and 55 extracellular metabolites following secretome exposure. Several metabolic pathways, including lactate, aminoacyl-tRNA biosynthesis, purine metabolism, and energy metabolism, were found to be dysregulated upon E. coli secretome exposure. E. coli can alter the breast cancer cells’ metabolism through its secretome which disrupts key metabolic pathways of MCF-7 cells. These microbial metabolites from the secretome hold promise as biomarkers of drug resistance or innovative approaches for cancer treatment, either as standalone therapies or in combination with other medicines. Full article
(This article belongs to the Special Issue Environmental Toxicology and Metabolism)
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11 pages, 2619 KiB  
Communication
Investigating the Acute Metabolic Effects of the N-Methyl Carbamate Insecticide, Methomyl, on Mouse Liver
by Amy M. Groswald, Tyler C. Gripshover, Walter H. Watson, Banrida Wahlang, Jianzhu Luo, Loretta L. Jophlin and Matthew C. Cave
Metabolites 2023, 13(8), 901; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo13080901 - 1 Aug 2023
Viewed by 1133
Abstract
Many pesticides have been identified as endocrine and metabolism-disrupting chemicals with hepatotoxic effects. However, data are limited for insecticides in the n-methyl carbamate class, including methomyl. Here, we investigate the liver and systemic metabolic effects of methomyl in a mouse model. We hypothesize [...] Read more.
Many pesticides have been identified as endocrine and metabolism-disrupting chemicals with hepatotoxic effects. However, data are limited for insecticides in the n-methyl carbamate class, including methomyl. Here, we investigate the liver and systemic metabolic effects of methomyl in a mouse model. We hypothesize that methomyl exposure will disrupt xenobiotic and intermediary metabolism and promote hepatic steatosis in mice. Male C57BL/6 mice were exposed daily to 0–5 mg/kg methomyl for 18 days. Mice were fed water and regular chow diet ad libitum. Metabolic phenotyping was performed, and tissue samples were collected. Effects were generally greatest at the highest methomyl dose, which induced Cyp1a2. Methomyl decreased whole body weight while the liver:body weight and testes:body weight ratios were increased. Hepatic steatosis increased while plasma LDL decreased. Fasting blood glucose and the glucose tolerance test area under the curve decreased along with hepatic glycogen stores. Methomyl, however, did not increase liver oxidative stress or injury. Collectively, these data demonstrate that methomyl disrupts hepatic xenobiotic and intermediary metabolism while increasing the testes:body weight ratio, suggesting that it may be an endocrine disrupting chemical. Besides methomyl’s known action in cholinesterase inhibition, it may be involved in aryl hydrocarbon receptor activation. The potential impact of n-methyl carbamate insecticides on metabolic health and diseases, including toxicant-associated steatotic liver disease (TASLD), warrants further investigation. Full article
(This article belongs to the Special Issue Environmental Toxicology and Metabolism)
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11 pages, 1293 KiB  
Article
Effects of Ecologically Relevant Concentrations of Cadmium on the Microbiota, Short-Chain Fatty Acids, and FFAR2 Expression in Zebrafish
by Jian Yang, Junyi Li, Xiaoshun Zhang, Qin Zhou, Junyi Wang, Qingsong Chen, Xiaojing Meng and Yuan Xia
Metabolites 2023, 13(5), 657; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo13050657 - 15 May 2023
Cited by 3 | Viewed by 1241
Abstract
Exposure to cadmium (Cd) can affect neurodevelopment and results in increased potential of developing neurodegenerative diseases during the early developmental stage of organisms, but the mechanisms through which exposure to environmentally relevant concentrations of Cd lead to developmental neurotoxicity remain unclear. Although we [...] Read more.
Exposure to cadmium (Cd) can affect neurodevelopment and results in increased potential of developing neurodegenerative diseases during the early developmental stage of organisms, but the mechanisms through which exposure to environmentally relevant concentrations of Cd lead to developmental neurotoxicity remain unclear. Although we know that microbial community fixations overlap with the neurodevelopmental window during early development and that Cd-induced neurodevelopmental toxicity may be related to the disruption of microorganisms during early development, information on the effects of exposure to environmentally relevant Cd concentrations on gut microbiota disruption and neurodevelopment is scarce. Therefore, we established a model of zebrafish exposed to Cd (5 µg/L) to observe the changes in the gut microbiota, SCFAs, and free fatty acid receptor 2 (FFAR2) in zebrafish larvae exposed to Cd for 7 days. Our results indicated that there were significant changes in the gut microbial composition due to the exposure to Cd in zebrafish larvae. At the genus level, there were decreases in the relative abundances of Phascolarctobacterium, Candidatus Saccharimonas, and Blautia in the Cd group. Our analysis revealed that the acetic acid concentration was decreased (p > 0.05) while the isobutyric acid concentration was increased (p < 0.05). Further correlation analysis indicated a positive correlation between the content of acetic acid and the relative abundances of Phascolarctobacterium and Candidatus Saccharimonas (R = 0.842, p < 0.01; R = 0.767, p < 0.01), and a negative correlation between that of isobutyric acid and the relative abundance of Blautia glucerasea (R = −0.673, p < 0.05). FFAR2 needs to be activated by SCFAs to exert physiological effects, and acetic acid is its main ligand. The FFAR2 expression and the acetic acid concentration were decreased in the Cd group. We speculate that FFAR2 may be implicated in the regulatory mechanism of the gut–brain axis in Cd-induced neurodevelopmental toxicity. Full article
(This article belongs to the Special Issue Environmental Toxicology and Metabolism)
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16 pages, 3193 KiB  
Article
The Specific Binding and Promotion Effect of Azoles on Human Aldo-Keto Reductase 7A2
by Wanying Wu, Tianqing Jiang, Haihui Lin, Chao Chen, Lingling Wang, Jikai Wen, Jun Wu and Yiqun Deng
Metabolites 2023, 13(5), 601; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo13050601 - 27 Apr 2023
Viewed by 1079
Abstract
Human AKR 7A2 broadly participates in the metabolism of a number of exogenous and endogenous compounds. Azoles are a class of clinically widely used antifungal drugs, which are usually metabolized by CYP 3A4, CYP2C19, and CYP1A1, etc. in vivo. The azole–protein interactions that [...] Read more.
Human AKR 7A2 broadly participates in the metabolism of a number of exogenous and endogenous compounds. Azoles are a class of clinically widely used antifungal drugs, which are usually metabolized by CYP 3A4, CYP2C19, and CYP1A1, etc. in vivo. The azole–protein interactions that human AKR7A2 participates in remain unreported. In this study, we investigated the effect of the representative azoles (miconazole, econazole, ketoconazole, fluconazole, itraconazole, voriconazole, and posaconazole) on the catalysis of human AKR7A2. The steady-state kinetics study showed that the catalytic efficiency of AKR7A2 enhanced in a dose-dependent manner in the presence of posaconazole, miconazole, fluconazole, and itraconazole, while it had no change in the presence of econazole, ketoconazole, and voriconazole. Biacore assays demonstrated that all seven azoles were able to specifically bind to AKR7A2, among which itraconazole, posaconazole, and voriconazole showed the strongest binding. Blind docking predicted that all azoles were apt to preferentially bind at the entrance of the substrate cavity of AKR7A2. Flexible docking showed that posaconazole, located at the region, can efficiently lower the binding energy of the substrate 2-CBA in the cavity compared to the case of no posaconazole. This study demonstrates that human AKR7A2 can interact with some azole drugs, and it also reveals that the enzyme activity can be regulated by some small molecules. These findings will enable a better understanding of azole–protein interactions. Full article
(This article belongs to the Special Issue Environmental Toxicology and Metabolism)
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25 pages, 3561 KiB  
Article
An Exploratory Study of the Metabolite Profiling from Pesticides Exposed Workers
by Daniela Magalhães Nolasco, Michele P. R. Mendes, Luiz Paulo de Aguiar Marciano, Luiz Filipe Costa, Adriana Nori De Macedo, Isarita Martins Sakakibara, Alessandra Cristina Pupin Silvério, Maria José N. Paiva and Leiliane C. André
Metabolites 2023, 13(5), 596; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo13050596 - 27 Apr 2023
Viewed by 1619
Abstract
Pesticides constitute a category of chemical products intended specifically for the control and mitigation of pests. With their constant increase in use, the risk to human health and the environment has increased proportionally due to occupational and environmental exposure to these compounds. The [...] Read more.
Pesticides constitute a category of chemical products intended specifically for the control and mitigation of pests. With their constant increase in use, the risk to human health and the environment has increased proportionally due to occupational and environmental exposure to these compounds. The use of these chemicals is associated with several toxic effects related to acute and chronic toxicity, such as infertility, hormonal disorders and cancer. The present work aimed to study the metabolic profile of individuals occupationally exposed to pesticides, using a metabolomics tool to identify potential new biomarkers. Metabolomics analysis was carried out on plasma and urine samples from individuals exposed and non-exposed occupationally, using liquid chromatography coupled with mass spectrometry (UPLC-MS). Non-targeted metabolomics analysis, using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) or partial least squares discriminant orthogonal analysis (OPLS-DA), demonstrated good separation of the samples and identified 21 discriminating metabolites in plasma and 17 in urine. The analysis of the ROC curve indicated the compounds with the greatest potential for biomarkers. Comprehensive analysis of the metabolic pathways influenced by exposure to pesticides revealed alterations, mainly in lipid and amino acid metabolism. This study indicates that the use of metabolomics provides important information about complex biological responses. Full article
(This article belongs to the Special Issue Environmental Toxicology and Metabolism)
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14 pages, 2005 KiB  
Article
Benzisothiazolinone: Pharmacokinetics, Tissue Distribution, and Mass Balance Studies in Rats
by Seong Jun Jo, Soo Hyeon Bae, Zhouchi Huang, Sangyoung Lee, Chae Bin Lee, Soon Uk Chae, Jung Bae Park, Mihye Kwon, Hye Kyung Chung and Soo Kyung Bae
Metabolites 2023, 13(5), 584; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo13050584 - 23 Apr 2023
Cited by 2 | Viewed by 1572
Abstract
Humans are continuously exposed to benzisothiazolinone (BIT), which is used as a preservative, through multiple routes. BIT is known to be a sensitizer; in particular, dermal contact or aerosol inhalation could affect the local toxicity. In this study, we evaluated the pharmacokinetic properties [...] Read more.
Humans are continuously exposed to benzisothiazolinone (BIT), which is used as a preservative, through multiple routes. BIT is known to be a sensitizer; in particular, dermal contact or aerosol inhalation could affect the local toxicity. In this study, we evaluated the pharmacokinetic properties of BIT in rats following various routes of administration. BIT levels were determined in rat plasma and tissues after oral inhalation and dermal application. Although the digestive system rapidly and completely absorbed orally administered BIT, it underwent severe first-pass effects that prevented high exposure. In an oral dose escalation study (5–50 mg/kg), nonlinear pharmacokinetic properties showed that Cmax and the area under the curve (AUC) increased more than dose proportionality. In the inhalation study, the lungs of rats exposed to BIT aerosols had higher BIT concentrations than the plasma. Additionally, the pharmacokinetic profile of BIT after the dermal application was different; continuous skin absorption without the first-pass effect led to a 2.13-fold increase in bioavailability compared with oral exposure to BIT. The [14C]-BIT mass balance study revealed that BIT was extensively metabolized and excreted in the urine. These results can be used in risk assessments to investigate the relationship between BIT exposure and hazardous potential. Full article
(This article belongs to the Special Issue Environmental Toxicology and Metabolism)
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15 pages, 2673 KiB  
Article
Microbial Virulence Factors, Antimicrobial Resistance Genes, Metabolites, and Synthetic Chemicals in Cabins of Commercial Aircraft
by Xi Fu, Mei Zhang, Yiwen Yuan, Yang Chen, Zheyuan Ou, Zailina Hashim, Jamal Hisham Hashim, Xin Zhang, Zhuohui Zhao, Dan Norbäck and Yu Sun
Metabolites 2023, 13(3), 343; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo13030343 - 24 Feb 2023
Cited by 1 | Viewed by 1575
Abstract
Passengers are at a higher risk of respiratory infections and chronic diseases due to microbial exposure in airline cabins. However, the presence of virulence factors (VFs), antimicrobial resistance genes (ARGs), metabolites, and chemicals are yet to be studied. To address this gap, we [...] Read more.
Passengers are at a higher risk of respiratory infections and chronic diseases due to microbial exposure in airline cabins. However, the presence of virulence factors (VFs), antimicrobial resistance genes (ARGs), metabolites, and chemicals are yet to be studied. To address this gap, we collected dust samples from the cabins of two airlines, one with textile seats (TSC) and one with leather seats (LSC), and analyzed the exposure using shotgun metagenomics and LC/MS. Results showed that the abundances of 17 VFs and 11 risk chemicals were significantly higher in TSC than LSC (p < 0.01). The predominant VFs in TSC were related to adherence, biofilm formation, and immune modulation, mainly derived from facultative pathogens such as Haemophilus parainfluenzae and Streptococcus pneumoniae. The predominant risk chemicals in TSC included pesticides/herbicides (carbofuran, bromacil, and propazine) and detergents (triethanolamine, diethanolamine, and diethyl phthalate). The abundances of these VFs and detergents followed the trend of TSC > LSC > school classrooms (p < 0.01), potentially explaining the higher incidence of infectious and chronic inflammatory diseases in aircraft. The level of ARGs in aircraft was similar to that in school environments. This is the first multi-omic survey in commercial aircraft, highlighting that surface material choice is a potential intervention strategy for improving passenger health. Full article
(This article belongs to the Special Issue Environmental Toxicology and Metabolism)
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