Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117306
Hong-fei Wang , Yu-qiong He , Zong Ke , Zhi-wei Liang , jia-hao Zhou , Ke Ni , Yu Zhang , Ren-feng Li , Jian-feng Xue , Can-can Zhou , Jia-Shuang Xu
Methotrexate (MTX), an anti-metabolite agent, is a widely used chemotherapeutic anticancer drug, but its hepatotoxicity severely limits its clinical application. Nevertheless, the precise mechanisms of MTX-caused liver damage are extremely intricate and still need to be fully clarified. In the current study, we investigated the role of the STING-ERS-ferroptosis axis in MTX-triggered hepatic toxicity in vivo and in vitro models. Male C57BL/6 J mice exposed to a single dose of MTX (0, 2, 5, and 20 mg/kg) for 3 days exhibited severe liver damage and overactivated STING signaling. Moreover, we found that ferroptosis was also involved in MTX-mediated liver damage. Interestingly, STING deficiency alleviated liver damage, inhibited liver inflammation, as well as suppressed hepatic lipid peroxidation and ferroptosis in MTX-treated mice. Consistently, STING inhibitor (C-176) pretreatment also alleviated MTX-induced STING signaling activation, ROS overproduction and ferroptosis in AML12 cells. Finally, we verified that ER stress was responsible for the MTX-induced liver injury and ferroptosis caused by STING activation. Taken together, our study uncovered a novel link between STING signaling and ferroptosis in MTX-triggered hepatic damages, and suggested that targeting the STING-ER stress-ferroptosis axis might be a promising and effective therapeutic approach against MTX-induced liver damage.
{"title":"STING signaling contributes to methotrexate-induced liver injury by regulating ferroptosis in mice","authors":"Hong-fei Wang , Yu-qiong He , Zong Ke , Zhi-wei Liang , jia-hao Zhou , Ke Ni , Yu Zhang , Ren-feng Li , Jian-feng Xue , Can-can Zhou , Jia-Shuang Xu","doi":"10.1016/j.ecoenv.2024.117306","DOIUrl":"10.1016/j.ecoenv.2024.117306","url":null,"abstract":"<div><div>Methotrexate (MTX), an anti-metabolite agent, is a widely used chemotherapeutic anticancer drug, but its hepatotoxicity severely limits its clinical application. Nevertheless, the precise mechanisms of MTX-caused liver damage are extremely intricate and still need to be fully clarified. In the current study, we investigated the role of the STING-ERS-ferroptosis axis in MTX-triggered hepatic toxicity in vivo and in vitro models. Male C57BL/6 J mice exposed to a single dose of MTX (0, 2, 5, and 20 mg/kg) for 3 days exhibited severe liver damage and overactivated STING signaling. Moreover, we found that ferroptosis was also involved in MTX-mediated liver damage. Interestingly, STING deficiency alleviated liver damage, inhibited liver inflammation, as well as suppressed hepatic lipid peroxidation and ferroptosis in MTX-treated mice. Consistently, STING inhibitor (C-176) pretreatment also alleviated MTX-induced STING signaling activation, ROS overproduction and ferroptosis in AML12 cells. Finally, we verified that ER stress was responsible for the MTX-induced liver injury and ferroptosis caused by STING activation. Taken together, our study uncovered a novel link between STING signaling and ferroptosis in MTX-triggered hepatic damages, and suggested that targeting the STING-ER stress-ferroptosis axis might be a promising and effective therapeutic approach against MTX-induced liver damage.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117306"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117340
Yixin Ma , Shixiong Li , Jingpeng Liu , Yuechen Sun , Yi Wu , Huangliang Chen , Meihan Mao , Wenlong Zhao , Chengcheng Deng , Jiefei Gao , Qitao Zhang , Jinrou Quan , Rui Qi
The study aimed to investigate the prevalence of antibiotic resistance genes (ARGs) within the ecosystem of natural plague foci, assessing their potential impact on the efficacy of plague treatments. Employing 16S rRNA gene sequencing and high-throughput quantitative PCR, microbial communities and ARGs were detected, with subsequent analysis of interactions among ARGs, mobile genetic elements (MGEs), environmental factors, and microbial species. Tetracycline resistance genes were found to be dominant, with multidrug and tetracycline resistance ARGs primarily associated with marmots and ecological soil, while pikas predominantly harbored β-lactam resistance ARGs. High detection rates were observed for resistance genes rpsl and sul1, which are relevant to streptomycin and sulfonamides, antibiotics commonly used in plague treatment. The total dissolved solids (TDS) in soil significantly promoted the presence of tetR-02, and Ni was found to inhibit vanHB. The tnpA-03 MGE was identified as a significant contributor to the dissemination of the aadE gene. The high prevalence of ARGs, particularly rpsl and sul1, poses a potential risk to the efficacy of main antibiotic treatments for plague. The study suggests that environmental microbiomes may be the greatest risk factor for the emergence of drug-resistant Yersinia pestis, given the low misuse of antibiotics in animals within natural plague foci. Monitoring the risk of drug-resistant strain emergence and preparing alternative antibiotic or combination therapy strategies based on ARG pollution levels in plague-affected areas is deemed necessary.
{"title":"Antibiotic resistance genes in plague ecosystems: Threatening the emergence of resistant plague","authors":"Yixin Ma , Shixiong Li , Jingpeng Liu , Yuechen Sun , Yi Wu , Huangliang Chen , Meihan Mao , Wenlong Zhao , Chengcheng Deng , Jiefei Gao , Qitao Zhang , Jinrou Quan , Rui Qi","doi":"10.1016/j.ecoenv.2024.117340","DOIUrl":"10.1016/j.ecoenv.2024.117340","url":null,"abstract":"<div><div>The study aimed to investigate the prevalence of antibiotic resistance genes (ARGs) within the ecosystem of natural plague foci, assessing their potential impact on the efficacy of plague treatments. Employing 16S rRNA gene sequencing and high-throughput quantitative PCR, microbial communities and ARGs were detected, with subsequent analysis of interactions among ARGs, mobile genetic elements (MGEs), environmental factors, and microbial species. Tetracycline resistance genes were found to be dominant, with multidrug and tetracycline resistance ARGs primarily associated with marmots and ecological soil, while pikas predominantly harbored β-lactam resistance ARGs. High detection rates were observed for resistance genes <em>rpsl</em> and <em>sul1</em>, which are relevant to streptomycin and sulfonamides, antibiotics commonly used in plague treatment. The total dissolved solids (TDS) in soil significantly promoted the presence of <em>tetR-02</em>, and Ni was found to inhibit <em>vanHB</em>. The <em>tnpA-03</em> MGE was identified as a significant contributor to the dissemination of the <em>aadE</em> gene. The high prevalence of ARGs, particularly <em>rpsl</em> and <em>sul1</em>, poses a potential risk to the efficacy of main antibiotic treatments for plague. The study suggests that environmental microbiomes may be the greatest risk factor for the emergence of drug-resistant <em>Yersinia pestis</em>, given the low misuse of antibiotics in animals within natural plague foci. Monitoring the risk of drug-resistant strain emergence and preparing alternative antibiotic or combination therapy strategies based on ARG pollution levels in plague-affected areas is deemed necessary.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117340"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117319
Luojia Li , Wei Luo , Pengyu Chen , Yujun Wang , Dan Liu , Yuzhou Lan , Xialin Chen , Lechan Zhou , Shiyong Yang , Zongjun Du
Given the reduction of freshwater resources, saline-alkaline aquaculture has emerged as an effective approach to expand the fishery's accessible space. High carbonate alkalinity (CA) is a major stressor for aquatic organisms in saline-alkaline environments. Paramisgurnus dabryanus is a potential species for culture in saline-alkaline water, making it an ideal model for investigating the physiological responses and tolerance mechanisms to CA exposure in freshwater fishes. In the current study, P. dabryanus were exposed to 15 and 30 mmol/L NaHCO3, combining blood biochemical, gill histological, transcriptomic, and metabolomic methods for conjoint analysis of response mechanisms. After 28-d exposure, the gill ventilation frequency of P. dabryanus decreased significantly, gill lamellae twisted and atrophied, and gill filament epithelial cells proliferated, potentially limiting gas exchange, whereas the accessory air-breathing frequency increased significantly, possibly for greater oxygen uptake. Serum osmolality and blood pH remained relatively steady, while serum ammonia levels rose significantly. A total of 3718 differentially expressed genes (DEGs) and 205 differential metabolites (DMs) were identified between the control group and 30 mmol/L NaHCO3 group, involved in ion transport (Na+/K+-ATPase, V-type ATPase, carbonic anhydrase, and ABC transporters), ammonia transport (Rh glycoproteins and Aquaporins), amino acid metabolism, carbohydrate metabolism, and fatty acid metabolism. Furthermore, DEGs were significantly associated with cell-cell/ extracellular matrix interaction and protein synthesis. An integrated multi-omics analysis revealed the activation of carbon metabolism and TCA cycle. These results indicate that in response to CA exposure, P. dabryanus may facilitate carrier-mediated ion and ammonia transport to maintain the internal osmotic equilibrium and lessen the deleterious effects of blocked ammonia excretion. Meanwhile, amino acid metabolism and protein synthesis are disturbed, P. dabryanus can modulate carbohydrate catabolism to maintain energy homeostasis. The above findings provide novel insights into saline-alkaline adaptation in freshwater fishes, paving the way for future research and development of saline-alkaline-tolerant Cobitidae strains.
{"title":"Study on the physiological responses and tolerance mechanisms to subchronic carbonate alkalinity exposure in the gills of Paramisgurnus dabryanus","authors":"Luojia Li , Wei Luo , Pengyu Chen , Yujun Wang , Dan Liu , Yuzhou Lan , Xialin Chen , Lechan Zhou , Shiyong Yang , Zongjun Du","doi":"10.1016/j.ecoenv.2024.117319","DOIUrl":"10.1016/j.ecoenv.2024.117319","url":null,"abstract":"<div><div>Given the reduction of freshwater resources, saline-alkaline aquaculture has emerged as an effective approach to expand the fishery's accessible space. High carbonate alkalinity (CA) is a major stressor for aquatic organisms in saline-alkaline environments. <em>Paramisgurnus dabryanus</em> is a potential species for culture in saline-alkaline water, making it an ideal model for investigating the physiological responses and tolerance mechanisms to CA exposure in freshwater fishes. In the current study, <em>P. dabryanus</em> were exposed to 15 and 30 mmol/L NaHCO<sub>3</sub>, combining blood biochemical, gill histological, transcriptomic, and metabolomic methods for conjoint analysis of response mechanisms. After 28-d exposure, the gill ventilation frequency of <em>P. dabryanus</em> decreased significantly, gill lamellae twisted and atrophied, and gill filament epithelial cells proliferated, potentially limiting gas exchange, whereas the accessory air-breathing frequency increased significantly, possibly for greater oxygen uptake. Serum osmolality and blood pH remained relatively steady, while serum ammonia levels rose significantly. A total of 3718 differentially expressed genes (DEGs) and 205 differential metabolites (DMs) were identified between the control group and 30 mmol/L NaHCO<sub>3</sub> group, involved in ion transport (Na<sup>+</sup>/K<sup>+</sup>-ATPase, V-type ATPase, carbonic anhydrase, and ABC transporters), ammonia transport (Rh glycoproteins and Aquaporins), amino acid metabolism, carbohydrate metabolism, and fatty acid metabolism. Furthermore, DEGs were significantly associated with cell-cell/ extracellular matrix interaction and protein synthesis. An integrated multi-omics analysis revealed the activation of carbon metabolism and TCA cycle. These results indicate that in response to CA exposure, <em>P. dabryanus</em> may facilitate carrier-mediated ion and ammonia transport to maintain the internal osmotic equilibrium and lessen the deleterious effects of blocked ammonia excretion. Meanwhile, amino acid metabolism and protein synthesis are disturbed, <em>P. dabryanus</em> can modulate carbohydrate catabolism to maintain energy homeostasis. The above findings provide novel insights into saline-alkaline adaptation in freshwater fishes, paving the way for future research and development of saline-alkaline-tolerant Cobitidae strains.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117319"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117293
Buyong Wang , Rongrong Wen , Xuenan Mao , Jie Chen , Xin Hao
Bursaphelenchus xylophilus is a pathogenic nematode responsible for pine wilt disease, which can cause the demise of pine trees and discoloration of trunks. As rotenone is an important botanical pesticide, its impact on B. xylophilus was investigated through RNA-seq to understand the response mechanism of nematode. The bioassay results yielded the 12-h LC30 (1.35 mg L−1) and LC50 (2.60 mg L−1) values for rotenone. Differential gene expression analysis identified 172 and 614 differentially expressed genes (DEGs) in B. xylophilus exposed to two different concentrations of rotenone (1.35 and 2.60 mg L−1). To validate these findings, the expression patterns of 10 DEGs were confirmed through RT-qPCR. Additionally, all DEGs were categorized into eight gene expression profiles using STEM. Notably, the gene ontology (GO) processes of "single-organism process," "metabolic process," and "catalytic activity" were prominently enriched in rotenone-treated samples, suggesting a role for metabolic and catalytic pathways in the nematode's response to rotenone stress. KEGG pathways related to "carbon metabolism," "drug metabolism-cytochrome P450," and "metabolism of xenobiotics by cytochrome P450" were similarly enriched, indicating potential mechanisms for detoxification resistance and oxidative stress resistance. The analysis pointed to the pivotal roles of detoxification- and oxidoreduction-related genes, as well as signal transduction-related genes, in enabling B. xylophilus to adapt to rotenone exposure. These insights could markedly enhance our understanding of nematode resistance mechanisms and potentially inform the development of more effective rotenone-based strategies for controlling B. xylophilus.
{"title":"Unveiling the co-expression network and molecular targets behind rotenone resistance in the Bursaphelenchus xylophilus","authors":"Buyong Wang , Rongrong Wen , Xuenan Mao , Jie Chen , Xin Hao","doi":"10.1016/j.ecoenv.2024.117293","DOIUrl":"10.1016/j.ecoenv.2024.117293","url":null,"abstract":"<div><div><em>Bursaphelenchus xylophilus</em> is a pathogenic nematode responsible for pine wilt disease, which can cause the demise of pine trees and discoloration of trunks. As rotenone is an important botanical pesticide, its impact on <em>B. xylophilus</em> was investigated through RNA-seq to understand the response mechanism of nematode. The bioassay results yielded the 12-h LC<sub>30</sub> (1.35 mg L<sup>−1</sup>) and LC<sub>50</sub> (2.60 mg L<sup>−1</sup>) values for rotenone. Differential gene expression analysis identified 172 and 614 differentially expressed genes (DEGs) in <em>B. xylophilus</em> exposed to two different concentrations of rotenone (1.35 and 2.60 mg L<sup>−1</sup>). To validate these findings, the expression patterns of 10 DEGs were confirmed through RT-qPCR. Additionally, all DEGs were categorized into eight gene expression profiles using STEM. Notably, the gene ontology (GO) processes of \"single-organism process,\" \"metabolic process,\" and \"catalytic activity\" were prominently enriched in rotenone-treated samples, suggesting a role for metabolic and catalytic pathways in the nematode's response to rotenone stress. KEGG pathways related to \"carbon metabolism,\" \"drug metabolism-cytochrome P450,\" and \"metabolism of xenobiotics by cytochrome P450\" were similarly enriched, indicating potential mechanisms for detoxification resistance and oxidative stress resistance. The analysis pointed to the pivotal roles of detoxification- and oxidoreduction-related genes, as well as signal transduction-related genes, in enabling <em>B. xylophilus</em> to adapt to rotenone exposure. These insights could markedly enhance our understanding of nematode resistance mechanisms and potentially inform the development of more effective rotenone-based strategies for controlling <em>B. xylophilus</em>.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117293"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117279
Liyaqat Ayoub , Munazah Yaqoob , Raihana H. Kanth , Fehim J. Wani , Zahoor Ahmad Shah , Eajaz Ahmad Dar , Fazil Fayaz Wani , Mohd Salim Mir , Nasir Bashir Naikoo , Audil Gull , Uzma Arifie , Yasmeen A. Alwasel , Mona S. Alwahibi
<div><div>European honey bee (<em>Apis mellifera</em> L.) is an essential pollinator that contributes significantly to the global ecosystem and agricultural productivity. However, their population has been facing unprecedented threats, primarily due to their exposure to various pesticides, including organophosphates. These pesticides are being widely used in agriculture to control insect pests due to their efficacy, but their non-selective nature raises concerns about their impact on honey bees. Insecticides <em>viz.,</em> chlorpyriphos 20 Emulsifiable Concentrate, dimethoate 30 Emulsifiable Concentrate, and profenophos 50 Emulsifiable Concentrate at a range of 0.005–0.09 per cent concentration were evaluated through two modes of application viz., topical and oral. Acetylcholinesterase (AChE) activity was measured at various intervals (1 and 24 hours) to assess enzyme inhibition. Behavioral observations and statistical analyses, including factor analysis with Eigen values, were employed to evaluate the impact of exposure on bee behavior and physiological responses.The results revealed two factors with Eigen value > 0.95 in both topical as well as oral method which accounted for 88.28 and 88.80 per cent of the variation in behaviour, respectively. Insecticides applied to honey bee <em>A. mellifera</em> in both topical as well as oral methods resulted in significant inhibition of the Acetyl choline esterase enzyme (AChE) activity. Studies revealed higher AChE inhibition (%) in oral method as compared to topical method. AChE inhibition percentage increased from 25.15 (1 Hour after treatment) to 58.25 (24 Hours after treatment) with lower concentration (0.005) of chlorpyriphos in topical method while as it reached from 27.66 to 60.94 with same concentration and same time in oral method of application. AChE inhibition percentage increased from 35.81 (1 Hour after treatment) to 78.30 (24 Hours after treatment) with higher concentration (0.06) of chlorpyriphos in topical method while as it reached from 40.35 to 80.18 with same concentration and same time in oral method. Similar trend was observed in dimethoate, and profenophos where AChE inhibition increased from 17.30, 27.15 (1 Hour after treatment) to 57.18, 61.81 (24 Hours after treatment), respectively in topical method and 20.67, 28.80 (1 Hour after treatment) to 59.85 64.04 (24 Hours after treatment), respectively in oral method. Similarly, with higher concentrations of dimethoate (0.07), and profenophos (0.09), per cent inhibition increased from 34.54, 38.60 (1 Hour after treatment) to 75.68, 79.62 (24 Hours after treatment), in topical method and 37.25, 41.23 (1 Hours after treatment) to 77.86, 82.73 (24 Hours after treatment), in oral method, respectively. Thorough risk assessments are vital for evaluating the effects of agrochemicals on <em>Apis mellifera</em>. The findings highlight the necessity for updated pesticide regulations and broadened conservation strategies that take into account
{"title":"Exposure to organophosphate insecticides induces behavioral changes and acetylcholinesterase inhibition in Apis mellifera","authors":"Liyaqat Ayoub , Munazah Yaqoob , Raihana H. Kanth , Fehim J. Wani , Zahoor Ahmad Shah , Eajaz Ahmad Dar , Fazil Fayaz Wani , Mohd Salim Mir , Nasir Bashir Naikoo , Audil Gull , Uzma Arifie , Yasmeen A. Alwasel , Mona S. Alwahibi","doi":"10.1016/j.ecoenv.2024.117279","DOIUrl":"10.1016/j.ecoenv.2024.117279","url":null,"abstract":"<div><div>European honey bee (<em>Apis mellifera</em> L.) is an essential pollinator that contributes significantly to the global ecosystem and agricultural productivity. However, their population has been facing unprecedented threats, primarily due to their exposure to various pesticides, including organophosphates. These pesticides are being widely used in agriculture to control insect pests due to their efficacy, but their non-selective nature raises concerns about their impact on honey bees. Insecticides <em>viz.,</em> chlorpyriphos 20 Emulsifiable Concentrate, dimethoate 30 Emulsifiable Concentrate, and profenophos 50 Emulsifiable Concentrate at a range of 0.005–0.09 per cent concentration were evaluated through two modes of application viz., topical and oral. Acetylcholinesterase (AChE) activity was measured at various intervals (1 and 24 hours) to assess enzyme inhibition. Behavioral observations and statistical analyses, including factor analysis with Eigen values, were employed to evaluate the impact of exposure on bee behavior and physiological responses.The results revealed two factors with Eigen value > 0.95 in both topical as well as oral method which accounted for 88.28 and 88.80 per cent of the variation in behaviour, respectively. Insecticides applied to honey bee <em>A. mellifera</em> in both topical as well as oral methods resulted in significant inhibition of the Acetyl choline esterase enzyme (AChE) activity. Studies revealed higher AChE inhibition (%) in oral method as compared to topical method. AChE inhibition percentage increased from 25.15 (1 Hour after treatment) to 58.25 (24 Hours after treatment) with lower concentration (0.005) of chlorpyriphos in topical method while as it reached from 27.66 to 60.94 with same concentration and same time in oral method of application. AChE inhibition percentage increased from 35.81 (1 Hour after treatment) to 78.30 (24 Hours after treatment) with higher concentration (0.06) of chlorpyriphos in topical method while as it reached from 40.35 to 80.18 with same concentration and same time in oral method. Similar trend was observed in dimethoate, and profenophos where AChE inhibition increased from 17.30, 27.15 (1 Hour after treatment) to 57.18, 61.81 (24 Hours after treatment), respectively in topical method and 20.67, 28.80 (1 Hour after treatment) to 59.85 64.04 (24 Hours after treatment), respectively in oral method. Similarly, with higher concentrations of dimethoate (0.07), and profenophos (0.09), per cent inhibition increased from 34.54, 38.60 (1 Hour after treatment) to 75.68, 79.62 (24 Hours after treatment), in topical method and 37.25, 41.23 (1 Hours after treatment) to 77.86, 82.73 (24 Hours after treatment), in oral method, respectively. Thorough risk assessments are vital for evaluating the effects of agrochemicals on <em>Apis mellifera</em>. The findings highlight the necessity for updated pesticide regulations and broadened conservation strategies that take into account","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117279"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117311
Haimin Song , Huaiyu Zhou , Shaochun Yang , Chunming He
Background
An increasing number of environmental pollutants are associated with human diseases. We explored the mechanisms by which an aromatic small molecule -- Methyl-4-hydroxybenzoate (MEP) contribute to the development of glioblastoma (GBM).
Methods
The causality of MEP and GBM were identified via the Mendelian Randomization (MR) analysis. We identified the key targets by integrating the targets of GBM, differential expressed genes (DEGs) from GEO and target genes of MEP. The network of hub genes was obtained from STRING and Cytoscape tools and GO, KEGG enrichment analysis were conducted by clusterProfiler R package. These hub targets were executed molecular docking via Autodock software.
Results
MEP had a causal association with GBM as risk factors (P < 0.05, OR > 1). 46 key targets were derived, in which CASP3, MMP2 and CDK4 were screened as the hub targets. MEP might play a role in the GBM by affecting the pathways of neuroactive ligand-receptor interaction, Molecular docking analysis showed a good binding ability of between MEP and CASP3, MMP2, CDK4, CASP8 and MCL1.
Conclusions
A causal relationship between MEP and GBM exists. CASP3, MMP2, CDK4, CASP8 and MCL1 have been identified as the crucial targets correlating with GBM. This discovery may provide an important insight into how environmental pollutants contribute to the development of GBM.
{"title":"Combining mendelian randomization analysis and network toxicology strategy to identify causality and underlying mechanisms of environmental pollutants with glioblastoma: A study of Methyl-4-hydroxybenzoate","authors":"Haimin Song , Huaiyu Zhou , Shaochun Yang , Chunming He","doi":"10.1016/j.ecoenv.2024.117311","DOIUrl":"10.1016/j.ecoenv.2024.117311","url":null,"abstract":"<div><h3>Background</h3><div>An increasing number of environmental pollutants are associated with human diseases. We explored the mechanisms by which an aromatic small molecule -- Methyl-4-hydroxybenzoate (MEP) contribute to the development of glioblastoma (GBM).</div></div><div><h3>Methods</h3><div>The causality of MEP and GBM were identified via the Mendelian Randomization (MR) analysis. We identified the key targets by integrating the targets of GBM, differential expressed genes (DEGs) from GEO and target genes of MEP. The network of hub genes was obtained from STRING and Cytoscape tools and GO, KEGG enrichment analysis were conducted by clusterProfiler R package. These hub targets were executed molecular docking via Autodock software.</div></div><div><h3>Results</h3><div>MEP had a causal association with GBM as risk factors (P < 0.05, OR > 1). 46 key targets were derived, in which CASP3, MMP2 and CDK4 were screened as the hub targets. MEP might play a role in the GBM by affecting the pathways of neuroactive ligand-receptor interaction, Molecular docking analysis showed a good binding ability of between MEP and CASP3, MMP2, CDK4, CASP8 and MCL1.</div></div><div><h3>Conclusions</h3><div>A causal relationship between MEP and GBM exists. CASP3, MMP2, CDK4, CASP8 and MCL1 have been identified as the crucial targets correlating with GBM. This discovery may provide an important insight into how environmental pollutants contribute to the development of GBM.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117311"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117313
Manman Hou , Pin Song , Yue Chen , Xiaoran Yang , Pengnan Chen , Aizhi Cao , Yingdong Ni
Subacute ruminal acidosis (SARA) is a common metabolic disease due to feeding high-concentrate (HC) diets to ruminants, especially dairy cows, in intensive farming system. Long term feeding HC diets commonly induce damages to hindgut barrier, leading to the translocation of harmful substances such as endotoxins (LPS) from lumen to blood, which results in a low-grade inflammation and stress response. Secondary bile acids (SBAs) play an important role in maintaining intestinal homeostasis. However, the function of SBAs on the intestinal epithelial barrier in SARA remains unclear. In this study, 15 growing goats were randomly divided into 3 groups, control group (30 % concentrate of dry matter, CON), SARA group (70 % concentrate of dry matter, SARA), and SARA+BAs group (70 % concentrate of dry matte, supplemented with 3 g/d/goat of BAs, SARA+BAs). The changes of mucosal permeability, gut microbiota and bile acids (BAs) profile was measured in the colon. The results showed that compared to CON group, the level of plasma D-lactate and diamine oxidase activity (DAO) (P < 0.05) was elevated in SARA group, while BAs supplementation significantly decreased plasma DAO (P < 0.05). The thickness of colonic mucosa, goblet cells (GCs) number (P < 0.01) and the abundance of MUC2 and occludin expression (P < 0.05) were significantly decreased in SARA group, while BAs supplementation markedly increased GCs number and improved mucosal barrier. BAs effectively reduced the content of LPS and volatile fatty acids (VFAs) in the colonic digesta (P < 0.05). Furthermore, BAs ameliorated SARA-induced reduction of total BAs (P < 0.001), primary BAs (P < 0.05), and conjugated BAs (P < 0.05) including taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA), as well as significantly increased hyodeoxycholic acid (HDCA) and lithocholic acid (LCA) contents in colonic digesta. 16S rRNA gene sequence analysis revealed that BAs decreased the abundance of Prevotella and Treponema, but increased the abundance of Akkermansia which was positively correlated with GCs number and MUC2 abundance. BAs supplementation improved the changes in the abundance of Roseburia, Negativibacillus, Lactobacillus, and unclassified_f_prevotellaceae, which were correlated with TCA, TCDCA, and TDCA levels. RNA-Seq results showed that, compared to SARA group, BAs activated the PPAR signaling pathway which was positively correlated with the number of GCs. In summary, BAs supplementation remodels the profiles of gut microbiota and metabolites, activates the PPAR signaling pathway, and eventually ameliorates intestinal mucosal barrier damage.
亚急性瘤胃酸中毒（SARA）是集约化养殖系统中反刍动物（尤其是奶牛）饲喂高浓缩（HC）日粮导致的一种常见代谢性疾病。长期饲喂高浓缩日粮通常会破坏后肠屏障，导致有害物质（如内毒素（LPS））从肠腔转移到血液中，从而引起低度炎症和应激反应。次级胆汁酸（SBAs）在维持肠道平衡方面发挥着重要作用。然而，SBAs 对 SARA 肠道上皮屏障的功能仍不清楚。本研究将 15 只生长中的山羊随机分为 3 组，即对照组（30% 干物质精料，CON）、SARA 组（70% 干物质精料，SARA）和 SARA+BAs 组（70% 干物质精料，添加 3 克/天/只 BAs，SARA+BAs）。测定了结肠粘膜渗透性、肠道微生物群和胆汁酸（BAs）谱的变化。结果表明，与 CON 组相比，SARA 组血浆 D-乳酸盐和二胺氧化酶活性（DAO）水平升高（P < 0.05），而补充 BAs 则显著降低血浆 DAO 水平（P < 0.05）。SARA组的结肠粘膜厚度、鹅口疮细胞（GCs）数量（P < 0.01）、MUC2丰度和闭塞素表达（P < 0.05）均明显降低，而补充BAs后GCs数量明显增加，粘膜屏障得到改善。BAs 能有效降低结肠消化液中 LPS 和挥发性脂肪酸（VFAs）的含量（P < 0.05）。此外，BAs还能改善SARA引起的结肠消化液中总BAs（P＜0.001）、原生BAs（P＜0.05）和共轭BAs（P＜0.05）（包括牛磺胆硷酸（TCA）、牛磺酸脱氧胆硷酸（TCDCA）和牛磺酸脱氧胆硷酸（TDCA））含量的减少，并显著增加透明脱氧胆硷酸（HDCA）和石胆酸（LCA）的含量。16S rRNA基因序列分析表明，BAs降低了普雷沃茨菌和特雷庞氏菌的丰度，但增加了阿克曼菌的丰度，而阿克曼菌的丰度与GCs数量和MUC2丰度呈正相关。补充 BAs 后，Roseburia、Negativibacillus、Lactobacillus 和未分类的_f_prevotellaceae 的丰度变化有所改善，这些变化与 TCA、TCDCA 和 TDCA 水平相关。RNA-Seq结果显示，与SARA组相比，BAs激活了PPAR信号通路，而PPAR信号通路与GC数量呈正相关。总之，补充 BAs 可重塑肠道微生物群和代谢物的特征，激活 PPAR 信号通路，并最终改善肠道粘膜屏障损伤。
{"title":"Bile acids supplementation improves colonic mucosal barrier via alteration of bile acids metabolism and gut microbiota composition in goats with subacute ruminal acidosis (SARA)","authors":"Manman Hou , Pin Song , Yue Chen , Xiaoran Yang , Pengnan Chen , Aizhi Cao , Yingdong Ni","doi":"10.1016/j.ecoenv.2024.117313","DOIUrl":"10.1016/j.ecoenv.2024.117313","url":null,"abstract":"<div><div>Subacute ruminal acidosis (SARA) is a common metabolic disease due to feeding high-concentrate (HC) diets to ruminants, especially dairy cows, in intensive farming system. Long term feeding HC diets commonly induce damages to hindgut barrier, leading to the translocation of harmful substances such as endotoxins (LPS) from lumen to blood, which results in a low-grade inflammation and stress response. Secondary bile acids (SBAs) play an important role in maintaining intestinal homeostasis. However, the function of SBAs on the intestinal epithelial barrier in SARA remains unclear. In this study, 15 growing goats were randomly divided into 3 groups, control group (30 % concentrate of dry matter, CON), SARA group (70 % concentrate of dry matter, SARA), and SARA+BAs group (70 % concentrate of dry matte, supplemented with 3 g/d/goat of BAs, SARA+BAs). The changes of mucosal permeability, gut microbiota and bile acids (BAs) profile was measured in the colon. The results showed that compared to CON group, the level of plasma D-lactate and diamine oxidase activity (DAO) (<em>P</em> < 0.05) was elevated in SARA group, while BAs supplementation significantly decreased plasma DAO (<em>P</em> < 0.05). The thickness of colonic mucosa, goblet cells (GCs) number (<em>P</em> < 0.01) and the abundance of MUC2 and occludin expression (<em>P</em> < 0.05) were significantly decreased in SARA group, while BAs supplementation markedly increased GCs number and improved mucosal barrier. BAs effectively reduced the content of LPS and volatile fatty acids (VFAs) in the colonic digesta (<em>P</em> < 0.05). Furthermore, BAs ameliorated SARA-induced reduction of total BAs (<em>P</em> < 0.001), primary BAs (<em>P</em> < 0.05), and conjugated BAs (<em>P</em> < 0.05) including taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA), as well as significantly increased hyodeoxycholic acid (HDCA) and lithocholic acid (LCA) contents in colonic digesta. 16S rRNA gene sequence analysis revealed that BAs decreased the abundance of <em>Prevotella</em> and <em>Treponema</em>, but increased the abundance of <em>Akkermansia</em> which was positively correlated with GCs number and MUC2 abundance. BAs supplementation improved the changes in the abundance of <em>Roseburia</em>, <em>Negativibacillus</em>, <em>Lactobacillus</em>, and <em>unclassified_f_prevotellaceae</em>, which were correlated with TCA, TCDCA, and TDCA levels. RNA-Seq results showed that, compared to SARA group, BAs activated the PPAR signaling pathway which was positively correlated with the number of GCs. In summary, BAs supplementation remodels the profiles of gut microbiota and metabolites, activates the PPAR signaling pathway, and eventually ameliorates intestinal mucosal barrier damage.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117313"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117275
Yao Xiong , Shaoyuan Xu , Ziwei Wang , Zihan Wang , Shuwei Li , Ming Zhang , Yuanzhen Zhang
Bisphenol A (BPA) exposure is linked to multiple adverse health outcomes, prompting the rise of "BPA-free" products. However, substitutes like Bisphenol S (BPS) and Bisphenol F (BPF) are equally prevalent, with detection frequencies and concentrations rivaling BPA. Our research previously identified BPA as an endocrine disruptor affecting reproductive and developmental systems. This study explores the impact of BPA, BPS, and BPF on endometrial decidualization and receptivity. We detected these bisphenols in serum samples from infertile women undergoing assisted reproductive technology (ART) treatment whose average age was 31.58 years. Human endometrial stromal cells were exposed to varying concentrations (0, 1 nM, 10 nM, 100 nM, and 1 µM) of BPA, BPS, and BPF, following hormonal induction of decidualization (10 nM E2 (Estradiol) + 0.5 mM cAMP (Cyclic adenosine monophosphate) + 1 µM MPA (Medroxyprogesterone acetate) for 6 days). Methods including CCK-8, RT-qPCR, untargeted metabolomics, and transcriptome sequencing assessed cell proliferation, molecular markers, gene expression, and metabolites. BPS levels in the serum of infertile patients were significantly higher than BPA (14.52 vs. 2.58 ng/mL) and even more pronounced in the recurrent implantation failure (RIF) group compared to the Control group (23.46 vs. 5.57 ng/mL). Findings revealed that BPA and its substitutes inhibited endometrial stromal cell proliferation and reduced decidualization markers. Differential metabolites (25, 66, 104) and gene expressions (3260, 9686, 10357) were observed with BPA, BPF, and BPS exposure, respectively. Enriched pathways included glutathione metabolism, arginine biosynthesis, ABC transporters, cAMP signaling, and glucagon signaling. Metabolomics and transcriptome analyses unveiled the reproductive toxic effects of BPA and its substitutes, suggesting significant impacts on endometrial decidualization through diverse signaling pathways.
双酚 A（BPA）暴露与多种不良健康后果有关，这促使 "不含 BPA "产品的兴起。然而，双酚 S (BPS) 和双酚 F (BPF) 等替代品同样普遍存在，其检测频率和浓度可与双酚 A 相媲美。我们之前的研究发现，双酚 A 是一种影响生殖和发育系统的内分泌干扰物。本研究探讨了双酚 A、双酚 BPS 和双酚 F 对子宫内膜蜕膜和接受能力的影响。我们在接受辅助生殖技术（ART）治疗的不孕妇女的血清样本中检测到了这些双酚，这些妇女的平均年龄为 31.58 岁。在激素诱导蜕膜化（10 nM E2（雌二醇）+ 0.5 mM cAMP（环磷酸腺苷）+ 1 µM MPA（醋酸甲羟孕酮），持续 6 天）后，人类子宫内膜基质细胞暴露于不同浓度（0、1 nM、10 nM、100 nM 和 1 µM）的双酚 A、双酚 BPS 和双酚 F。包括 CCK-8、RT-qPCR、非靶向代谢组学和转录组测序在内的方法对细胞增殖、分子标记物、基因表达和代谢物进行了评估。不孕症患者血清中的双酚A水平明显高于双酚A（14.52 vs. 2.58 ng/mL），与对照组（23.46 vs. 5.57 ng/mL）相比，复发性植入失败（RIF）组的双酚A水平更高。研究结果表明，双酚 A 及其替代品抑制了子宫内膜基质细胞的增殖，并降低了蜕膜化标志物。在暴露于双酚 A、双酚 F 和双酚 S 的情况下，分别观察到不同的代谢物（25、66、104）和基因表达（3260、9686、10357）。丰富的途径包括谷胱甘肽代谢、精氨酸生物合成、ABC 转运体、cAMP 信号转导和胰高血糖素信号转导。代谢组学和转录组分析揭示了双酚 A 及其替代品的生殖毒性效应，表明它们通过不同的信号通路对子宫内膜的蜕变产生了重大影响。
{"title":"BPA-free? Exploring the reproductive toxicity of BPA substitutes BPS and BPF on endometrial decidualization","authors":"Yao Xiong , Shaoyuan Xu , Ziwei Wang , Zihan Wang , Shuwei Li , Ming Zhang , Yuanzhen Zhang","doi":"10.1016/j.ecoenv.2024.117275","DOIUrl":"10.1016/j.ecoenv.2024.117275","url":null,"abstract":"<div><div>Bisphenol A (BPA) exposure is linked to multiple adverse health outcomes, prompting the rise of \"BPA-free\" products. However, substitutes like Bisphenol S (BPS) and Bisphenol F (BPF) are equally prevalent, with detection frequencies and concentrations rivaling BPA. Our research previously identified BPA as an endocrine disruptor affecting reproductive and developmental systems. This study explores the impact of BPA, BPS, and BPF on endometrial decidualization and receptivity. We detected these bisphenols in serum samples from infertile women undergoing assisted reproductive technology (ART) treatment whose average age was 31.58 years. Human endometrial stromal cells were exposed to varying concentrations (0, 1 nM, 10 nM, 100 nM, and 1 µM) of BPA, BPS, and BPF, following hormonal induction of decidualization (10 nM E2 (Estradiol) + 0.5 mM cAMP (Cyclic adenosine monophosphate) + 1 µM MPA (Medroxyprogesterone acetate) for 6 days). Methods including CCK-8, RT-qPCR, untargeted metabolomics, and transcriptome sequencing assessed cell proliferation, molecular markers, gene expression, and metabolites. BPS levels in the serum of infertile patients were significantly higher than BPA (14.52 vs. 2.58 ng/mL) and even more pronounced in the recurrent implantation failure (RIF) group compared to the Control group (23.46 vs. 5.57 ng/mL). Findings revealed that BPA and its substitutes inhibited endometrial stromal cell proliferation and reduced decidualization markers. Differential metabolites (25, 66, 104) and gene expressions (3260, 9686, 10357) were observed with BPA, BPF, and BPS exposure, respectively. Enriched pathways included glutathione metabolism, arginine biosynthesis, ABC transporters, cAMP signaling, and glucagon signaling. Metabolomics and transcriptome analyses unveiled the reproductive toxic effects of BPA and its substitutes, suggesting significant impacts on endometrial decidualization through diverse signaling pathways.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117275"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117296
Kanchana RK. Dilrukshi , Ilaria R. Merutka , Melissa Chernick , Stephanie Rohrbach , Remy Babich , Niroshan Withanage , Pani W. Fernando , Nishad Jayasundara
Mixtures of chemical contaminants can pose a significant health risk to humans and wildlife, even at levels considered safe for each individual chemical. There is a critical need to develop statistical methods to evaluate the drivers of toxic effects in chemical mixtures (i.e., bad actors) from exposure studies. Here, we develop a hierarchical modeling framework to disentangle the toxicity of complex metal mixtures from a screening study of 92 drinking well water samples containing multiple metal elements from Maine and New Hampshire, USA. In order to screen for neurodevelopmental impacts from exposure to these drinking water samples, we use a larval zebrafish (Danio rerio) behavioral assay. Zebrafish are an advantageous toxicological model organism due to combining the complexity of a vertebrate organism and higher-throughput exposure methods. We formulate a linear mixed modeling approach that captures intrinsic complexity in a common larval behavioral assay in order to improve its sensitivity and rigor and identify drivers of behavioral toxicity from the metal mixtures within the drinking water samples. Our analysis identifies lead (Pb), cadmium (Cd), nickel (Ni), copper (Cu), barium (Ba), and uranium (U) as metals that consistently impact larval locomotor activity, individually and across nine pairs of those metals. Our model also elucidates three distinct clusters of metal mixture components that drive behavioral effects: (Ba:Cu:U), (Ni:Pb:U), (Ba:Pb:U). Having identified a set of “bad-actor” metals from the water samples, we conduct exposure experiments for each individual metal (Pb, Cd, Ni, Cu, and Ba) at levels considered safe by the US Environmental Protection Agency drinking water regulatory limits and validate Pb, Ni, Cu, and Ba as behavioral toxicants at these concentrations. Collectively, our modeling approach estimates the impact of metal elements on a complex behavioral outcome in a statistically robust manner and establishes an approach to capture “bad actors” and key chemical interactions in a complex mixture.
{"title":"Determining bad actors: A linear mixed effects model approach to elucidate behavioral toxicity of metal mixtures in drinking water","authors":"Kanchana RK. Dilrukshi , Ilaria R. Merutka , Melissa Chernick , Stephanie Rohrbach , Remy Babich , Niroshan Withanage , Pani W. Fernando , Nishad Jayasundara","doi":"10.1016/j.ecoenv.2024.117296","DOIUrl":"10.1016/j.ecoenv.2024.117296","url":null,"abstract":"<div><div>Mixtures of chemical contaminants can pose a significant health risk to humans and wildlife, even at levels considered safe for each individual chemical. There is a critical need to develop statistical methods to evaluate the drivers of toxic effects in chemical mixtures (i.e., bad actors) from exposure studies. Here, we develop a hierarchical modeling framework to disentangle the toxicity of complex metal mixtures from a screening study of 92 drinking well water samples containing multiple metal elements from Maine and New Hampshire, USA. In order to screen for neurodevelopmental impacts from exposure to these drinking water samples, we use a larval zebrafish (<em>Danio rerio</em>) behavioral assay. Zebrafish are an advantageous toxicological model organism due to combining the complexity of a vertebrate organism and higher-throughput exposure methods. We formulate a linear mixed modeling approach that captures intrinsic complexity in a common larval behavioral assay in order to improve its sensitivity and rigor and identify drivers of behavioral toxicity from the metal mixtures within the drinking water samples. Our analysis identifies lead (Pb), cadmium (Cd), nickel (Ni), copper (Cu), barium (Ba), and uranium (U) as metals that consistently impact larval locomotor activity, individually and across nine pairs of those metals. Our model also elucidates three distinct clusters of metal mixture components that drive behavioral effects: (Ba:Cu:U), (Ni:Pb:U), (Ba:Pb:U). Having identified a set of “bad-actor” metals from the water samples, we conduct exposure experiments for each individual metal (Pb, Cd, Ni, Cu, and Ba) at levels considered safe by the US Environmental Protection Agency drinking water regulatory limits and validate Pb, Ni, Cu, and Ba as behavioral toxicants at these concentrations. Collectively, our modeling approach estimates the impact of metal elements on a complex behavioral outcome in a statistically robust manner and establishes an approach to capture “bad actors” and key chemical interactions in a complex mixture.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117296"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ecoenv.2024.117271
Bohao Yin , Chenjun Liu , Hui Sun , Wei Zhang
Tetrabromobisphenol A (TBBPA) is a widely used flame retardant. TBBPA is a persistent pollutant that is difficult to degrade and causes sustained pollution to the environment. TBBPA has been detected in human blood and tissues, and studies indicate it causes various toxicological damages to tissues and cells. To date, the toxicological effects of TBBPA on chondrocytes are not fully understood. Here, we evaluated the toxicological effects of TBBPA on chondrocytes and tissues. For this, human- and mouse-derived chondrocyte models were used to analyze the toxicological effects of TBBPA. Physiological concentrations of TBBPA were used to stimulate chondrocytes. Indirect immunofluorescence, flow cytometry, and biochemical assays were utilized to investigate TBBPA's toxicological impact on chondrocytes. The CCK8 experiment indicated that TBBPA reduced chondrocyte proliferation. ELISA and Western blot results indicated that TBBPA increased inflammatory factor expression in chondrocytes. We also found that TBBPA caused oxidative stress in chondrocytes. Mechanistic study showed that TBBPA triggered a imbalance in the homeostasis of calcium ions, leading to mitochondrial depolarization, which induces inflammation and oxidative stress of chondrocytes. In vivo model, our research showed that TBBPA caused inflammation in knee joint cartilage. Safranin O-Fast Green and H&E staining revealed cartilage tissue damage following TBBPA treatment. TBBPA increased MMP9 and MMP13 expression and down-regulated COL2 expression. In summary, we assessed TBBPA's impact on chondrocytes. The experimental data indicate that TBBPA causes damage to chondrocytes. This study establishes a basis for future research on the toxicological impacts of TBBPA.
{"title":"TBBPA exposure causes cartilage cell damage in both in vitro and in vivo models","authors":"Bohao Yin , Chenjun Liu , Hui Sun , Wei Zhang","doi":"10.1016/j.ecoenv.2024.117271","DOIUrl":"10.1016/j.ecoenv.2024.117271","url":null,"abstract":"<div><div>Tetrabromobisphenol A (TBBPA) is a widely used flame retardant. TBBPA is a persistent pollutant that is difficult to degrade and causes sustained pollution to the environment. TBBPA has been detected in human blood and tissues, and studies indicate it causes various toxicological damages to tissues and cells. To date, the toxicological effects of TBBPA on chondrocytes are not fully understood. Here, we evaluated the toxicological effects of TBBPA on chondrocytes and tissues. For this, human- and mouse-derived chondrocyte models were used to analyze the toxicological effects of TBBPA. Physiological concentrations of TBBPA were used to stimulate chondrocytes. Indirect immunofluorescence, flow cytometry, and biochemical assays were utilized to investigate TBBPA's toxicological impact on chondrocytes. The CCK8 experiment indicated that TBBPA reduced chondrocyte proliferation. ELISA and Western blot results indicated that TBBPA increased inflammatory factor expression in chondrocytes. We also found that TBBPA caused oxidative stress in chondrocytes. Mechanistic study showed that TBBPA triggered a imbalance in the homeostasis of calcium ions, leading to mitochondrial depolarization, which induces inflammation and oxidative stress of chondrocytes. <em>In vivo</em> model, our research showed that TBBPA caused inflammation in knee joint cartilage. Safranin O-Fast Green and H&E staining revealed cartilage tissue damage following TBBPA treatment. TBBPA increased MMP9 and MMP13 expression and down-regulated COL2 expression. In summary, we assessed TBBPA's impact on chondrocytes. The experimental data indicate that TBBPA causes damage to chondrocytes. This study establishes a basis for future research on the toxicological impacts of TBBPA.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117271"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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