ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
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2019
·Vol. 38
·期 10
·2169-2177
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IF 3.421
An He,Xinyong Liu,Liang Qu,Yongfei Gao,Jianfeng Feng,Lin Zhu
We exposed zebrafish ( Danio rerio ) to different concentrations of lead and cadmium, and monitored them for survival at 24, 48, 72, and 96 h. Metal toxicity was predicted and compared using the dose–response and general threshold survival models in terms of required data sets, fit performance, and applicability. Environ Toxicol Chem 2019;38:2169–2177. © 2019 SETAC.
研究领域:
环境毒理学
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生态学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chen Li,Zhu Ruiqin,Ma Yaxing,Huang Chuixiu,Shen Xiantao
Objective: LC-MS/MS-based metabolomics is an important tool for studying disease-related biomarkers. Conventionally, different strategies have been used to screen biomarkers. However, many studies for biomarker screening by different strategies have ignored the dose-response relationship between the biomarker level and exposure level, and no relevant studies have described and compared different strategies in detail. Phenobarbital (PHB) which belongs to the barbiturates, was selected as the typical representative of neurotoxins. Acylcarnitines have been promising candidates for diagnostic biomarkers for several neurological disorders and neurotoxicity. In this work, we aimed to use an acute PHB poisoning animal model to clarify PHB poisoning effects on plasma and brain acylcarnitine changes and how to rationally analyze data from LC-MS/MS.Methods: The acylcarnitine profiles in plasma and brain regions in an actuate PHB poisoning animal model were utilized. The dose-response relationship between plasma PHB and carnitine and acylcarnitines (CARs) in plasma and brain were assessed by the variance analysis trend test and Spearman’s rank correlation test. In different strategies, principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA) screened the differential CARs, variable importance plots (VIPs) were utilized to select putative biomarkers for PHB-induced toxicity, and receiver operating characteristic (ROC) curve analysis then illustrated the reliability of biomarkers.Results: Under the first strategy, 14 potential toxicity biomarkers were obtained including eight downregulated CARs with AUC >0.8. Under the second strategy, 11 potential toxicity biomarkers were obtained containing five downregulated CARs with AUC >0.8. Only when the dose-response relationship was fully considered, different strategies screen for the same biomarkers (plasma acetyl-carnitine (C2) and plasma decanoyl-carnitine (C10)), which indicated plasma acylcarnitines might serve as toxicity biomarkers. In addition, the plasma CAR level changes showed differences from brain CAR level changes, and correlations between plasma CARs and their brain counterparts were weak.Conclusion: We found that plasma C2 and C10 might serve as toxicity biomarkers for PHB poisoning disorders, and PHB poisoning effects on changes in plasma CARs may not be fully representative of changes in brain CARs.
研究领域:
代谢组学
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神经毒理学
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医学
✓ 已验证
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2021
·
IF 7.963
Hongyan Shen,Yingying Liu,Yinan Liu,Zemeng Duan,Pengpeng Wu,Zhifen Lin,Haoyu Sun
Silver antibacterial compounds (SACs) and quorum sensing inhibitors (QSIs), as the potential antibiotic substitutes, have been recommended to prevent and treat microbial infections for the purpose of controlling the increasingly serious bacterial resistance induced by the abuse of antibiotics. However, there is little information regarding the resistance risk of these compounds, especially their mixtures. In this study, bacterial mutation and RP4 plasmid conjugative transfer among bacteria were used to characterize the bacterial endogenous and exogenous resistance, respectively. The effects of SACs (including silver nitrate (AgNO 3 ) and silver nanoparticle (AgNP)), QSIs, and their binary mixtures on the bacterial resistance were investigated via setting the frequency of mutation and conjugative transfer in Escherichia coli ( E. coli ) as the test endpoints. The results indicated that these two endpoints exhibited hormetic dose-responses to each treatment. Furthermore, the joint resistance actions between SACs and QSIs were all judged to be antagonism. Correlation analysis suggested that the promotion of the bacterial resistance in each treatment was closely related to its toxicity. It was speculated that AgNO 3 and AgNP might both release Ag + ions to facilitate the E. coli resistance, while QSIs probably acted on LsrR and SdiA proteins to stimulate the bacterial mutation and accelerate the RP4 plasmid conjugative transfer, respectively. These findings imply that the bacteria may generate targeted stress response to the survival pressure from environmental compounds, displaying hormetic phenomenon in resistance-related test endpoints. This study provides a new insight into the resistance risk induced by SACs and QSIs, benefiting the environmental risk assessment of these compounds from the perspective of bacterial resistance.
研究领域:
微生物学
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环境科学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2019
·
IF 5.108
Xiaoxian Zhang,Zhifen Lin
Guidelines of ecological risk assessment (ERA) used worldwide, based on S-shaped threshold dose-response curve, fail to consider hormesis, a biphasic dose-response model represented as a J-shaped or an inverted U-shaped curve, that occurs in real-life environment. Now that humans are routinely exposed to chemicals below the threshold where hormetic stimulation prevails, it is noteworthy that over-strictness about chemical control also means a waste of limited resources. So hormesis leads to the gap between guidelines with S-shaped model and reality with hormesis model concerning ERA. In this study, hormetic effects of sulfachloropyridazine (SCP) on the bioluminescence of Aliivibrio fischeri ( A. f ) under 41 conditions to simulate the real environment were investigated and compared with ERA practice by some parameters, such as no observed effect concentration (NOEC), hormetic-stimulatory range (HSR) and goal concentration (GC). Not only is the reproducibility of hormesis in real-life contexts confirmed, binomial distribution (p = 0.644 > 0.05) of the relative position of GC and HSR is also found, revealing a 50% probability for GC to falls in HSR, which proves the over-strictness of ERA both qualitatively and quantitatively. This study provides a novel view for ERA that hormetic principles should dominate, and conditions where S-shaped dose-response model works should be singled out on a specific basis to bridge the hormesis-induced gap.
研究领域:
环境科学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Miao Yang,Yuxuan Lu,Weifeng Mao,Liping Hao
PAH4 (sum of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene) has been proposed as better marker than benzo[a]pyrene to assess total PAHs exposure in foodstuffs. However, the toxicological behaviors of PAH4 combined exposure remain unclear. This study aimed to investigate PAH4 toxicity effects with non-targeted metabolomics approach and evaluate the external and internal dose-response relationships based on benchmark dose (BMD) analysis. Male Sprague-Dawley rats were treated by gavage with vehicle (corn oil) or four doses of PAH4 (10, 50, 250, 1000 μg/kg·bw) for consecutive 30 days. After the final dose, the liver, blood and urine samples of rats were subsequently collected for testing. The concentrations of urinary mono-hydroxylated PAHs metabolites (OH-PAHs) including 3-hydroxybenzo[a]pyrene (3-OHB[a]P), 3-hydroxychrysene (3-OHCHR) and 3-hydroxybenz[a]anthracene (3-OHB[a]A) were determined to reflect internal PAH4 exposure. Our results showed PAH4 exposure increased relative liver weight and serum aspartate aminotransferase (AST) activity and caused hepatocyte swelling and degeneration, implying hepatotoxicity induced by PAH4. Serum metabolomics suggested PAH4 exposure perturbed lipid metabolism through upregulating the expression of glycerolipids metabolites, which was evidenced by markedly increased serum triglyceride (TG) level and hepatic TG content. Additionally, urinary OH-PAHs concentrations presented strong positive correlations with the external dose, indicating they were able to reflect PAH4 exposure. Furthermore, PAH4 exposure led to a dose-response increase of hepatic TG content, based on which the 95% lower confidence value of BMDs for external and internal doses were estimated as 5.45 μg/kg·bw and 0.11 μmol/mol·Cr, respectively. In conclusion, this study suggested PAH4 exposure could induce hepatotoxicity and lipid metabolism disorder, evaluating the involved dose-response relationships and providing a basis for the risk assessment of PAHs.
研究领域:
毒理学
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环境健康
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2020
·
IF 4.902
Yuqi Yang,Yiyue Guo,You Xu,Yingying Meng,Xing Zhang,Xuejun Xia,YuLing Liu
Deformable nanovesicles (DNVs) have been used in the buccal delivery of biomacromolecules due to their ability to enhance drug penetration. However, no breakthroughs have been made until now due to limited understanding of the factors affecting in vivo buccal delivery. In this study, we designed a series of DNVs, based on an insulin–phospholipid complex (IPC-DNVs), to investigate the influence of drug dose, buccal administration methods, and key quality characteristics of IPC-DNVs for buccal delivery. IPC-DNVs showed a non-linear dose–response relationship between 8 and 12 IU. There was no significant effect of drug delivery site (sublingual mucosa/buccal mucosa) or ligation time (15 or 30 min) on buccal absorption of IPC-DNVs. However, the area above the curve of reduction in blood glucose level overtime (AAC0–6h) for oral mucosa administration was significantly higher than that for buccal mucosa administration. Increasing the drug concentration in IPC-DNVs led to a decrease in AAC0–6h. This might be due to local leakage of DNVs, while squeezing through biological barriers with high concentration of insulin, thus hindering the subsequent delivery of DNVs. IPC-DNVs, measuring 80–220 nm in size, did not significantly affect AAC0–6h. However, when the size was increased to approximately 400 nm, AAC0–6h decreased, thus suggesting that IPC-DNVs with reasonable size were more effective. Additionally, increased deformability of IPC-DNVs might cause drugs to leak easily, thus reducing the promoting effect of buccal absorption. Our results clarified the effect of characteristics of IPC-DNVs on buccal delivery in vivo and provided meaningful support for the design of dosage form of DNVs.
研究领域:
药剂学
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生物医学工程
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药物传递系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2022
·
IF 14.224
Wan Yang,Chen Cai,Rui Wang,Xiaohu Dai
Wide commercial applications of antimicrobial quaternary ammonium compounds (QACs) inevitably lead to the release into wastewater and enrichment in sewage sludge . This study evaluated the impacts of levels and structures of QACs on sewage sludge properties, microbial community , and methane production during anaerobic digestion . Methane production was stimulated or not affected at low QACs concentrations, but significantly inhibited at high QACs concentrations. Compared with benzyl and alkyltrimethyl QACs, dialkyl QACs showed least toxicity on digestion performance. Meanwhile, microbial community analysis indicated that shifts in bacterial communities mainly depended on QACs doses, but the archaeal communities were affected by both QACs doses and types. The dominant methanogenic pathway shifted from acetotrophic/methylotrophic methanogens to mixotrophic methanogens by low levels of benzyl and alkyltrimethyl QACs but not dialkyl QACs, and further to hydrogenotrophic methanogens at high QACs concentration. Mechanism exploration revealed that the presence of QACs promoted sludge solubilization by the integrated effects of cell lysis, electric neutralization, and hydrophobicity improvement, but inhibited methanogenesis due to the accumulation of volatile fatty acids and susceptibility of methanogens to QACs. These findings provided a reference for potential impacts of different QACs on sludge biological treatment, which had implications for the use and selection of QACs disinfectants.
研究领域:
环境工程
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微生物学
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废物管理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2022
·
IF 10.753
Yiwei Fang,Zhiliang Chen,Jinyu Chen,Minqi Zhou,Yuanyao Chen,Rong Cao,Chunyan Liu,Kai Zhao,Min Wang,Huiping Zhang
Mono(2-ethylhexyl) phthalate (MEHP) is a metabolite of DEHP which is one of phthalic acid esters (PAEs) widely used in daily necessities. Moreover, MEHP has been proven to have stronger biological toxicity comparing to DEHP. In particular, several recent population-based studies have reported that intrauterine exposure to MEHP results in adverse pregnancy outcomes. To explore the mechanisms and metabolic biomarkers of MEHP exposure, we examined the metabolic status of HTR-8/Svneo cell lines exposed to different doses of MEHP (0, 1.25, 5.0, 20 μM). Global and dose–response metabolomics tools were used to identify metabolic perturbations and sensitive markers associated with MEHP. Only 22 metabolic features (accounted for <1 %) were significantly changed when exposed to 1.25 μM. However, when the exposure dose was increased to 5 or 20 μM, the number of significantly changed metabolic features exceeded 300 (approximately 10 %). In particular, amino acid metabolism, pyrimidine metabolism and glutathione metabolism were widely affected according to the enrich analysis of those significant altered metabolites, which has and have previously been reported to be closely related to fetal development. Moreover, 5′-UMP and N -acetylputrescine with the lowest effective concentrations (EC −10 = 0.1 μM and EC +10 = 0.11 μM, respectively) were identified as sensitive endogenous biomarkers of MEHP exposure.
研究领域:
毒理学
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生殖生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MethodsX
·
2022
·
IF 0
Liang Tang,Danqing Tong,Yulian Zhang,Jiajun Wang,Haoyu Sun
The severe pollution of bacterial resistance induced by the wide and even indiscriminate use of antibacterial agents has posed serious threats to human health and ecological safety. Furthermore, the combined effects of antibacterial agents have a closer relationship with the pollution of bacterial resistance than single antibacterial agent. However, there is little information regarding how multiple antibacterial agents interplay to induce bacterial resistance. Here, we developed a simple judgment method with five basic procedures for the joint action of antibacterial agents on bacterial resistance, involving toxicity determination, mutation frequency determination, conjugative transfer frequency determination, dose-response relationship fitting, key parameters obtaining, and joint resistance action judgment. This proposed approach was validated through investigating the joint resistance action between silver nanoparticle (AgNP) and 1-pyrrolidino-1-cyclohexene (1P1C, a kind of quorum sensing inhibitors). According to the procedures, the mutation unit and conjugative transfer unit for the AgNP-1P1C mixture were calculated to be 64.27 and 5.10, respectively, indicating the antagonism for their joint resistance action. This method can not only benefit the mechanistic explanation for how mixed antibacterial agents stimulate the bacterial resistance, but also guide the environmental risk assessment and clinical use of combined antibacterial agents in the related fields. • We present a novel method to judge the joint resistance action of antibacterial agents, taking the emergence and dissemination of antibiotic resistance genes into account. • Toxicity determination can help to design the mixtures of antibacterial agents and confirm the appropriate test concentration range of antibacterial agents used in mutation frequency and conjugative transfer frequency determination. • The mutation unit and conjugative transfer unit were proposed according to the toxic unit in the judgment of joint toxic action.
研究领域:
微生物学
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环境科学
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药理学
✓ 已验证
DOI
PubMed
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2017
·
IF 2.313
Sen Zhang,Huan Chen,An Wang,Yong Liu,Hongwei Hou,Qingyuan Hu
To evaluate the genotoxic effects of formaldehyde, acetaldehyde, acrolein and benzene on A549 cells, the in vitro γH2AX assay was used in combination with high content screening (HCS) technology. All aldehydes showed a significant genotoxicity in a dose/time-dependent effect on the induction of γH2AX. Benzene failed to show a significant genotoxicity based on the γH2AX assay. However, hydroquinone (one of metabolites of benzene) showed a significant genotoxicity in vitro. Based on the dose-response of γH2AX and Hill model, the ability to induce DNA double-strand break can be evaluated as acrolein > formaldehyde > acetaldehyde > benzene. The slow DNA damage/repair mechanism may be more important than the fast one for aldehydes based on time-course of γH2AX and two-component model. Overall, all toxicants were genotoxic in a dose- or time-dependent manner based on the in vitro γH2AX HCS assay, and acrolein had a strong potential to induce DNA damage followed by formaldehyde, acetaldehyde and benzene in sequence.
研究领域:
毒理学
·
分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Xuewen Yao,Zhaokang Cheng,Evgenios Agathokleous,Yaqian Wei,Xinyuan Feng,Hanhan Li,Tingting Zhang,Shuting Li,Gaurav Dhawan,Xiao-San Luo
As typical antibiotics, tetracycline (TC) and sulfadiazine (SDZ) enter the human body through the food chain. Therefore, it is necessary to understand their individual and combined toxicity. In this study, the effects of TC, SDZ, and their mixture on cell viability, cell membrane damage, liver cell damage, and oxidative damage were evaluated in in vitro assays with human liver cells Huh-7. The results showed cytotoxicity of TC, SDZ, and their mixture, which induced oxidative stress and caused membrane and cell damage. The effect of antibiotics on Huh-7 cells increased with increasing concentration, except for lactate dehydrogenase (LDH) activity that commonly showed a threshold concentration response and cell viability, which commonly showed a biphasic trend, suggesting the possibility of hormetic responses where proper doses are included. The toxicity of TC was commonly higher than that of SDZ when applied at the same concentration. These findings shed light on the individual and joint effects of these major antibiotics on liver cells, providing a scientific basis for the evaluation of antibiotic toxicity and associated risks.
研究领域:
药理学
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毒理学
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细胞生物学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2021
·
IF 7.086
Ze-Jun Wang,Qiao-Feng Zheng,Shu-Shen Liu,Peng Huang,Ting-Ting Ding,Ya-Qian Xu
At present, the toxicity prediction of mixtures mainly focuses on the concentration addition (CA) and independent action (IA) based on individual toxicants to predict the toxicity of multicomponent mixtures. This process of predicting the toxicity of multicomponent mixtures based on single substances or low component mixtures is called down-to-top method in this study. However, due to the particularity of some toxicants, we have to use the top-to-down idea to obtain or eliminate the toxicity of some components from mixtures. For example, the toxicity of toxicants is obtained from the toxicity of a mixture with, especially toxic, cosolvent added. In the study, two top-to-down methods, the inverse CA (ICA) and inverse IA (IIA) models, were proposed to eliminate the effects of a certain component from multicomponent mixtures. Furthermore, taking the eight binary mixtures consisting of different shapes of cosolvents (isopropyl alcohol (IPA) having hormesis and dimethyl sulfoxide (DMSO)) and toxicants (two ionic liquids and two pesticides) as an example, combined with the interaction evaluated by CA and IA model, the influence of different shapes of components on top-to-down toxicity prediction was explored. The results showed that cosolvent IPA having hormesis may cause unpredictable effects, even at low concentrations, and should be used with caution. For DMSO, most of the toxicant's toxicity obtained by ICA and IIA models were almost in accordance with those observed experimentally, which showed that ICA and IIA could effectively eliminate the effects of cosolvent, even if toxic cosolvent, from the mixture. Ultimately, a frame of cosolvent use and toxicity correction for the hydrophobic toxicant were suggested based on the top-to-down toxicity prediction method. The proposed methods improve the existing framework of mixture toxicity prediction and provide a new idea for mixture toxicity evaluation and risk assessment.
研究领域:
环境毒理学
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风险评估
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化学毒理学
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药学
✓ 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）