MARINE POLLUTION BULLETIN
·
2020
·
IF 4.049
Lefei Jiao,Tianmeng Dai,Tinglan Cao,Min Jin,Peng Sun,Qicun Zhou
Heavy metal pollution arising from agricultural and industrial activities poses a significant threat to the aquatic environment, especially the increasing levels of chromium (Cr) that is exacerbating marine pollution. Given the economic importance of the Pacific white shrimp Litopenaeus vannamei ( L. vannamei ), understanding the impact of marine Cr pollution is deemed to be significant. In this study, we used the transcriptome sequencing (RNA-seq) technique to characterize the molecular mechanism of Cr exposure in L. vannamei . Gene ontology enrichment analysis showed substrate-specific and ion transport-related functions were mainly influenced by Cr exposure. We further identified genes involved in protein digestion and absorption (PEPT1, BAT1, MDU1), chemical carcinogenesis (GST and UGTs), ABC transporters (ABCC2), apoptosis (CAPN1, CASP10, PARP), implying the potentially Cr disintoxication mechanisms in L. vannamei . Genes within pancreatic secretion (ALT, LDH), lysosome (CTSL and HEXB), and peroxisome (ACOX1, ECI2, NUDT12) pathways implied the potentially Cr toxicity mechanisms in L. vannamei .
研究领域:
环境科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Di Cui,Peng Zhang,Haipu Li,Zhaoxue Zhang,Wenbao Luo,Zhaoguang Yang
The metabolic process and toxicity mechanism of dietary inorganic arsenic (iAs) in freshwater fish remain unclear to date. The present study conducted two iAs [arsenate (As(V)) and arsenite (As(III))] dietary exposures in freshwater fish crucian carp ( Carassius auratus ). The fish were fed on As supplemented artificial diets at nominal concentrations of 50 and 100 μg As(III) or As(V) g −1 (dry weight) for 10 d and 20 d. We found that the liver, kidney, spleen, and intestine of fish accumulated more As in As(V) feeding group than that in As(III), while the total As levels in muscle were similar between As(V) and As(III) group at the end of exposure. Reduction of As(V) to As(III) and oxidation of As(III) to As(V) occurred in fish fed with As(V) and As(III), respectively, indicating that toxicity of iAs was likely elevated or reduced when iAs was absorbed by fish before entering into human body through diet. Biomethylation to monomethylarsonic acid and dimethylarsinic acid and transformation to arsenocholine and arsenobetaine were also found in the fish. The linear regression analysis showed a positive correlation between secondary methylation index and the malondialdehyde content in tissues, highlighting the vital role of arsenic dimethylation in the oxidative damages in fish.
研究领域:
环境毒理学
·
水生生物学
·
鱼类生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Xianbin Su,Teng Li,Xiaowen Zhu,Peihua Zheng,Huakang Pan,Hui Guo
Nonylphenol (NP) is one of the common pollutants in the environment that have toxic effects on aquatic animals. Nevertheless, little is known about the possible toxicity mechanism of NP on the hepatopancreas of Litopenaeus vannamei . In the present study, the detrimental effects of NP on the hepatopancreas of the L. vannamei were explored at the histological and transcriptomic levels. The findings indicated that after NP exposed for 3, 12, and 48 h, the hepatopancreas histology was changed significantly. Transcriptomic analysis showed that a total of 4302, 3651, and 4830 differentially expressed genes (DEGs) were identified at 3, 12, and 48 h following NP exposure. All these DEGs were classified into 12 clusters according to the expression patterns at different time points. GO and KEGG enrichment analyses of DEGs were also performed, immunological, metabolic, and inflammatory related pathways, including arachidonic acid metabolism (ko00590), the PPAR signaling pathway (ko03320), and the regulation of TRP channels by inflammatory mediators (ko04750) were significantly enriched. Six DEGs were selected for validation by quantitative real-time PCR (qRT-PCR) and the results confirmed the reliability of transcriptome data. All results indicated that NP is toxic to L. vannamei by damaging the histopathological structure and disrupting the biological function. The findings would provide a theoretical framework for lowering or limiting the detrimental impacts of NP on aquaculture and help us to further study the molecular toxicity of NP in crustaceans.
研究领域:
水产养殖学
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环境毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2019
·
IF 7.149
Ge Liu,Ruifen Jiang,Jing You,Derek C. G. Muir,Eddy Y. Zeng
Research has already demonstrated the toxic effects of microplastics (MPs) on different biota. However, the underlying toxic mechanism of MPs remains to be elucidated, especially the effect of particle size and the presence of dissolved organic matter in water. This study investigated the impact on Scenedesmus obliquus exposed in five types of polystyrene particle suspensions with different sizes and surface charges, in the presence and absence of humic acid (HA). Results indicated that the 50% growth inhibition rate of S. obliquus showed no significant difference between the five types of MPs, but the toxic mechanism varied with particle size. Larger size MPs caused adverse effects by blocking the light transport and affecting photosynthesis, while smaller ones destroyed the cell wall by adsorbing onto the algae surface. Also, the addition of HA significantly alleviated the toxicity of smaller size MPs, but not of the larger ones. Scanning electron microscopy images and the reactive oxygen species assay demonstrated that the HA could form a corona on the surface of MPs, reduce the affinity to microalgae, and minimize the adverse effect. Together, these findings identified important factors in determining the toxicity of MPs, providing valuable data for risk assessment of MPs.
研究领域:
环境生物学
·
生态毒理学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Dong Li,Wen Cheng,Xiaoping Zhou,Xing Zheng,Jiehui Ren,Ting Meng
Chloro-haloacetonitrile (Cl-HAN), belongs to a group of nitrogenous disinfection by-products (N-DBPs) found in surface water, and are known to pose a major risk to the safety of human drinking water. However, the exact biological toxicity mechanism and the extent of the stress response caused by Cl-HAN remain unclear, resulting in a lack of effective measures to control its presence. Thus, the quantitative toxicological genomics and bioinformatics methods were applied to explore the effects of three chloro-haloacetonitriles (Cl-HANs) on the transcription of fusion genes under varying concentrations of stress in E. coli over 2-hour period. The initial stress response and their toxic mechanism were analyzed. The study also identified the molecular toxicity endpoint, and the core genes that are responsible for the specific toxicity of different Cl-HANs. Cl-HANs exhibited concentration-dependent characteristics of toxic effects, and caused changes in gene expression related oxidative and membrane stress. The stress response results showed that dichloroacetonitrile (dCAN) still caused significant DNA damage under the lowest concentration stress. Chloroacetonitrile (CAN) and trichloroacetonitrile (tCAN) exhibited lower genetic toxicity levels at 513 μg/L and 10.7 μg/L, respectively. The toxic effects of tCAN were widespread. And there was a good correlation between the molecular endpoint (EC-TELI 1.5 ) and the phenotypic endpoint (LD50) with r p =-0.8634 ( P =0.0593). In all concentrations of stress in CAN, dCAN, and tCAN, the number of overexpressed genes shared was 15, 2, and 14, respectively. Furthermore, bioinformatics analysis demonstrated that Cl-HANs affected genes associated with general stress pathways, such as cell biochemistry and physical homeostasis, resulting in changes in biological processes. And for CAN-induced DNA damage, polA played a dominant role, while katG , oxyR , and ahpC were the core genes involved in oxidative stress induced by dCAN and tCAN, respectively. These findings provide valuable data for the toxic effect of Cl-HANs.
研究领域:
环境科学
·
分子生物学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2022
·Vol. 29
·期 27
·41439-41454
·
IF 5.19
Liu Chengkun,Shi Kailun,Lyu Keliang,Liu Dongwu,Wang Xue
The wide usage of neodymium (Nd) in industry, agriculture, and medicine has made it become an emerging pollutant in the environment. Increasing Nd pollution has potential hazards to plants, animals, and microorganisms. Thus, it is necessary to study the toxicity of Nd and the mechanism of Nd transportation and detoxification in microorganisms. Through genome-scale screening, we identified 70 yeast monogene deletion mutations sensitive to Nd ions. These genes are mainly involved in metabolism, transcription, protein synthesis, cell cycle, DNA processing, protein folding, modification, and cell transport processes. Furthermore, the regulatory networks of Nd toxicity were identified by using the protein interaction group analysis. These networks are associated with various signal pathways, including calcium ion transport, phosphate pathways, vesicular transport, and cell autophagy. In addition, the content of Nd ions in yeast was detected by an inductively coupled plasma mass spectrometry, and most of these Nd-sensitive mutants showed an increased intracellular Nd content. In all, our results provide the basis for understanding the molecular mechanisms of detoxifying Nd ions in yeast cells, which will be useful for future studies on Nd-related issues in the environment, agriculture, and human health.
研究领域:
分子生物学
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环境科学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Jin J. Li,Ya X. Yue,Jie F. Jiang,Sheng J. Shi,Hui X. Wu,Yuan H. Zhao,Fei F. Che
Antibiotics have received much attention owing to their ecotoxicity toward nontarget aquatic creatures. However, the mode of action (MOA) of toxicity against nontarget organisms is unclear in some aquatic organisms. In this study, the comparison of toxicities through interspecies correlations, excess toxicity calculated from toxicity ratio, and quantitative structure-activity relationship (QSAR) was carried out to investigate the MOAs for 14 antibiotics among Daphnia magna , Vibrio fischeri, and Pseudokirchneriella subcapitata . The results showed that interspecies toxicity correlations were very poor between any two of the three species for the 14 antibiotics. The toxicity ratio revealed that most antibiotics exhibited excess toxicity to algae and Daphnia magna but not to V. fischeri , demonstrating that some antibiotics share the same MOA, but some antibiotics share different MOAs among the three different levels of species. P. subcapitata was the most sensitive species, and V. fischeri was the least sensitive species. This is because of the differences in the biouptake and interactions of antibiotics with the target receptors between the three different trophic levels of the species. Molecular docking simulations suggested that the toxicity of antibiotics depends highly on their interactions with target receptors through hydrogen bonds , electrostatic or polar interactions, π bond interactions, and van der Waals forces . QSAR models demonstrated that hydrogen bonding and electrophilicity/nucleophilicity play key roles in the interaction of antibiotics with different receptors in the three species. The toxic mechanisms of antibiotics are attributed to the interactions between electrophilic antibiotics and biological nucleophiles , and hydrogen-bond interactions. These results are valuable for understanding the toxic mechanisms and MOA of the three different levels of species.
研究领域:
生态毒理学
·
环境科学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2016
·Vol. 408
·期 15
·4111-4119
·
IF 3.125
Xie Honglei,Liu Yuyang,Peng Ying,Zhao Dongmei,Zheng Jiang
Dauricine is a bisbenzylisoquinoline alkaloid derivative and has shown multiple pharmacological properties. Despite this, our previous study demonstrated that dauricine induced severe lung toxicity in experimental animals. Metabolic activation of dauricine to the corresponding quinone methide intermediate is suggested to play an important role in dauricine-induced cytotoxicity. Protein adduction derived from the reactive intermediate is considered to initiate the process of the toxicity. In the present study, we developed an alkaline permethylation- and mass spectrometry-based approach to detect dauricine-derived protein adduction. Protein samples were permethylated in the presence of NaOH and CH 3 I at 80 °C, followed by LC-MS/MS analysis. A thioether product was produced in the reaction. Not only does this technique quantify dauricine-derived protein adduction but also it tells the nature of the interaction between the target proteins and the reactive intermediate of dauricine. The recovery, precision, limit of detection, limit of quantity, and method detection limit were found to be 102.8 %±1.7 %, 1.89 %, 1.32 fmol/mL, 4.93 fmol/mL and 3.37 fmol/mL respectively. The surrogate recovery and surrogate RSD values were 81.5–103.0 % and 2.59 %, respectively. This analytical method has proven sensitive, selective, reliable, and feasible to assess total protein adduction derived from dauricine, and will facilitate the mechanistic investigation of dauricine and other bisbenzylisoquinoline toxicities.
Alkaline permethylation of dauricine derived protein adduct
研究领域:
药理学
·
毒理学
·
蛋白质组学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Yuezhu Wang,Yichi Zhang,Junsheng Wang,Weibing Liu,Huan Wang,Mingzhu Song,Hongyue Zhang,Xin Wang
Algal toxins produced by microalgae, such as domoic acid (DA) 1 , have toxic effects on humans. However, toxicity tests using mice only yield lethal doses of algal toxins without providing insights into the mechanism of action on cells. In this study, a fast segmentation of microfluidic flow cytometry cell images based on the bidirectional background subtraction (BBS) 2 method was developed to get the visual evidence of apoptosis in both bright-field and fluorescence images. This approach enables mapping of changes in cell morphology and activity under algal toxins, allowing for fast (within 60 s) and automated biological detection. By combining microfluidics with flow cytometry, the intricate cellular-level reaction process can be observed in micro samples of 293 T cells and mouse spleen cells, offering potential for future in vitro experiments.
研究领域:
生物学
·
毒理学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 32
·
IF 12.5
Runchuan Yan,Yan Zhang,Jingjing Zhang,Xiangyi Zhang,Yue Han,Mengfei Wang,Dan Wang,Shengnan Huang,Wei Liu,Qi Shi,Xiaoping Dong,Wen-Quan Zou,Zhen Li,Jiyan Ma
Rapid neurodegeneration distinguishes prion disease from other neurodegenerative disorders. Notably, normal prion protein (PrP C ) is essential for prion-induced rapid neurodegeneration, but the underlying mechanism remains unknown. Here, we show that the unstructured N-terminal region of PrP C induces rapid and lethal neurodegeneration in mice, accompanied by the hallmark of prion disease, spongiosis. The neurotoxic N-terminal PrP is soluble, associates peripherally with lipid membranes, and induces neurotoxicity only when a critical threshold is exceeded. Both the N-terminally localized KKRPKP sequence and octarepeats contribute to neurotoxicity, with KKRPKP being essential. Without it, the N-terminal PrP is innocuous but exacerbates either neurodegeneration caused by N-terminal PrP or neurodegeneration in prion disease induced by intracerebral prion inoculation in mice. Our findings establish that soluble N-terminal PrP causes rapid neurodegeneration in prion disease and is a target for intervention.
研究领域:
神经生物学
·
分子生物学
·
病理学
·
转化医学
·
蛋白质错误折叠疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2021
·
IF 3.739
Jiaxing He,Mingyue Liu,Lingfeng Yin,Ziqi Deng,Junhong Pang,Haoxian He,Li Dang,Ming-De Li
Carprofen (CP), one kind of a nonsteroidal anti-inflammatory drug, exhibits phototoxic side effects in physiology, while its phototoxic mechanism is ambiguous. To uncover CP’s photophysical and photochemical reaction processes, femtosecond to nanosecond transient absorption spectroscopies were employed to directly detect excited states and transient intermediates of CP upon UV irradiation in pure acetonitrile (MeCN), MeCN/water 1:1, and acid/alkaline buffer solutions. The transient absorption data together with DFT calculations were integrated to elucidate mechanisms for photochemical reactions of CP in different solutions. The associated photophysical and photochemical reaction pathways are dependent on various solution environments. In a pure MeCN solvent, CP is excited to a singlet state (S1) and rapidly interacts with the solvent to proceed solvent rearrangement (SR). It then undergoes vibrational cooling (VC) and proceeds intersystem crossing (ISC) to produce the lowest triplet state (3CP). 3CP finally decays to the ground state. While in a MeCN/water 1:1 solution, deprotonated S1 of CP experiences SR and VC processes, and then it is promoted to a deprotonated triplet state (3CP–). 3CP– undergoes the parallel reactions: dechlorination to a phenyl radical (2CP–) and decarboxylation to a T1 anion (3CP–(de-CO2)). Finally, both intermediates produce the radical anion species 2CP–(de-CO2). In a pH = 7.4 (MeCN/PBS 1:1) solution, 3CP– can be converted into 2CP–(de-CO2) more quickly. Interestingly, we found that the dechlorination step can be promoted in an alkaline solution. Phenyl and chlorine radicals produced in an aqueous solution may be the root cause of the drug’s harmful side effects on the human body. This may be useful to guide the design of related CP drugs with minimal phototoxicity in the pharmaceutical process.
研究领域:
药理学
·
光化学
·
理论化学
✓ 已验证
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2021
·
IF 7.963
Fanglin Shen,Dan Li,Jianmin Chen
Fuel exhaust particulate matter (FEPM) is an important source of air pollution worldwide. However, the comparative and mechanistic toxicity of FEPMs emitted from combustion of different fuels is still not fully understood. This study employed pathway-based approaches via human cells to evaluate mechanistic toxicity of FEPMs. The results showed that FEPMs caused concentration-dependent (0.1–200 μg/mL) cytotoxicity and oxidative stress. FEPMs at low concentration (10 μg/mL) induced cell cycle arrest in S and G2 phases, while high level of FEPMs (200 μg/mL) caused cell cycle arrest in G1 phase. Different FEPMs induced distinct expression profiles of toxicity-related genes, illustrating different toxic mechanisms. Furthermore, FEPMs inhibited the phosphorylation of protein kinase A (PKA), which related with reproductive toxicity. Spearman rank correlations among the chemicals carried by FEPMs and the toxic effects revealed that PAHs and metals promoted cell cycle arrest in the G1 phase and suppressed PKA activity. Furthermore, PAHs (Nap and Acy) and metals (Al and Pb) in FEPMs were highly and positively correlated with the expression of genes involved in apoptosis, ER stress, metal stress and inflammation. Our findings offered more mechanistic information of FEPMs at the level of subcellular toxicity and help to better understand their potential health effects.
研究领域:
环境科学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）