Chemical Research in Toxicology最新文献

{"title":"Molecular Insights into Propofol's Neurotoxic Effects: Targeting the HTR1A/cAMP Signaling Pathway.","authors":"Gongrui Zhou, Shubin Zheng, Yuhai Xu","doi":"10.1021/acs.chemrestox.4c00339","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00339","url":null,"abstract":"<p><p>Propofol, a commonly used anesthetic in clinical practice, is favored for its rapid onset and short duration of action. Despite its widespread use, the potential neurotoxic effects of propofol remain insufficiently understood. This study utilized high-throughput transcriptome sequencing and network pharmacology to investigate the mechanisms by which propofol induces neurotoxicity in rat hippocampal neural progenitor cells (NPCs), focusing on the HTR1A/cAMP signaling pathway. Our findings reveal that propofol significantly inhibits the HTR1A/cAMP pathway, leading to altered expression of key genes that affect neuronal activity, inflammatory responses, and apoptosis. In vivo experiments further demonstrate that propofol impairs spatial learning and memory in rats, an effect that is partially reversed by overexpression of HTR1A. These results not only elucidate the molecular mechanisms underlying propofol-induced neuronal damage but also provide critical insights into the safe application of propofol in clinical settings.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Insights into Propofol’s Neurotoxic Effects: Targeting the HTR1A/cAMP Signaling Pathway","authors":"Gongrui Zhou,&nbsp;Shubin Zheng and Yuhai Xu*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0033910.1021/acs.chemrestox.4c00339","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00339https://doi.org/10.1021/acs.chemrestox.4c00339","url":null,"abstract":"<p >Propofol, a commonly used anesthetic in clinical practice, is favored for its rapid onset and short duration of action. Despite its widespread use, the potential neurotoxic effects of propofol remain insufficiently understood. This study utilized high-throughput transcriptome sequencing and network pharmacology to investigate the mechanisms by which propofol induces neurotoxicity in rat hippocampal neural progenitor cells (NPCs), focusing on the HTR1A/cAMP signaling pathway. Our findings reveal that propofol significantly inhibits the HTR1A/cAMP pathway, leading to altered expression of key genes that affect neuronal activity, inflammatory responses, and apoptosis. In vivo experiments further demonstrate that propofol impairs spatial learning and memory in rats, an effect that is partially reversed by overexpression of HTR1A. These results not only elucidate the molecular mechanisms underlying propofol-induced neuronal damage but also provide critical insights into the safe application of propofol in clinical settings.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 4","pages":"561–572 561–572"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diallyl Disulfide Reduces Ethyl Carbamate-Induced Cytotoxicity and Apoptosis in Intestinal and Hepatic Cells","authors":"Caroline Andolfato Sanchez*,&nbsp;Estefani Maria Treviso,&nbsp;Cecília Cristina de Souza Rocha and Lusânia Maria Greggi Antunes*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0043910.1021/acs.chemrestox.4c00439","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00439https://doi.org/10.1021/acs.chemrestox.4c00439","url":null,"abstract":"<p >Epidemiological studies indicate that lifestyle and dietary habits are associated with an increasing cancer incidence. Consuming fermented foods and alcoholic beverages and smoking can expose humans to ethyl carbamate (EC), a probable human carcinogen classified as group 2A by the International Agency for Research on Cancer (IARC). Increasing the intake of bioactive compounds can reduce EC-induced toxicity. Diallyl disulfide (DADS), found in garlic, may protect against damage induced by chemical agents and natural compounds. Here, the potential protective effect of DADS against EC was investigated by evaluating EC-induced cytotoxicity, DNA damage, apoptosis, and reactive oxygen species production in colorectal adenocarcinoma (Caco-2) and hepatocarcinoma (HepG2) cells. To this end, resazurin, comet, and annexin V-FITC staining assays and CM-H₂DCFDA markers were used to evaluate the effect on Caco-2 and HepG2 cells of protocols combining DADS (10–120 μM) and EC (80 mM). The protocols were as follows: (i) cells pretreated with DADS for 2 h and exposed to EC for 24 h; (ii) cells pretreated with DADS for 24 h and exposed to EC for 24 h; (iii) cells simultaneously exposed to DADS and EC for 24 h; (iv) cells exposed to EC for 24 h and treated with DADS for 2 h. EC induced cytotoxicity and apoptosis in Caco-2 and HepG2 cells and oxidative damage in Caco-2 cells. Combined exposure to DADS and EC for 24 h decreased EC-mediated cytotoxicity and apoptosis in both Caco-2 and HepG2 cells. These findings encourage further studies on the mechanisms of action of the combined DADS and EC.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 4","pages":"623–634 623–634"},"PeriodicalIF":3.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrestox.4c00439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DICTrank Is a Reliable Dataset for Cardiotoxicity Prediction Using Machine Learning Methods.","authors":"Yanyan Qu, Ting Li, Zhichao Liu, Weida Tong, Dongying Li","doi":"10.1021/acs.chemrestox.4c00428","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00428","url":null,"abstract":"<p><p>Drug-induced cardiotoxicity (DICT) is a significant challenge in drug development and public health. DICT can arise from various mechanisms; New Approach Methods (NAMs), including quantitative structure-activity relationships (QSARs), have been extensively developed to predict DICT based solely on individual mechanisms (e.g., hERG-related cardiotoxicity) due to the availability of datasets limited to specific mechanisms. While these efforts have significantly contributed to our understanding of cardiotoxicity, DICT assessment remains challenging, suggesting that approaches focusing on isolated mechanisms may not provide a comprehensive evaluation. To address this, we previously developed DICTrank, the largest dataset for assessing overall cardiotoxicity liability in humans based on FDA drug labels. In this study, we evaluated the utility of DICTrank for QSAR modeling using five machine learning methods─Logistic Regression (LR), K-Nearest Neighbors, Support Vector Machines, Random Forest (RF), and extreme gradient boosting (XGBoost)─which vary in algorithmic complexity and explainability. To reflect real-world scenarios, models were trained on drugs approved before and within 2005 to predict the DICT risk of those approved thereafter. While we observed no clear association between prediction performance and model complexity, LR and XGBoost achieved the best results with DICTrank. Additionally, our significant-feature analyses with RF and XGBoost models provided novel insights into DICT mechanisms, revealing that drug properties associated with descriptors such as \"structural and topological\", \"polarizability\", and \"electronegativity\" contributed significantly to DICT. Moreover, we found that model performance varied by therapeutic category, suggesting the need to tailor models accordingly. In conclusion, our study demonstrated the robustness and reliability of DICTrank for cardiotoxicity prediction in humans using machine learning methods.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DICTrank Is a Reliable Dataset for Cardiotoxicity Prediction Using Machine Learning Methods","authors":"Yanyan Qu,&nbsp;Ting Li,&nbsp;Zhichao Liu,&nbsp;Weida Tong* and Dongying Li*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0042810.1021/acs.chemrestox.4c00428","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00428https://doi.org/10.1021/acs.chemrestox.4c00428","url":null,"abstract":"<p >Drug-induced cardiotoxicity (DICT) is a significant challenge in drug development and public health. DICT can arise from various mechanisms; New Approach Methods (NAMs), including quantitative structure–activity relationships (QSARs), have been extensively developed to predict DICT based solely on individual mechanisms (e.g., hERG-related cardiotoxicity) due to the availability of datasets limited to specific mechanisms. While these efforts have significantly contributed to our understanding of cardiotoxicity, DICT assessment remains challenging, suggesting that approaches focusing on isolated mechanisms may not provide a comprehensive evaluation. To address this, we previously developed DICTrank, the largest dataset for assessing overall cardiotoxicity liability in humans based on FDA drug labels. In this study, we evaluated the utility of DICTrank for QSAR modeling using five machine learning methods─Logistic Regression (LR), K-Nearest Neighbors, Support Vector Machines, Random Forest (RF), and extreme gradient boosting (XGBoost)─which vary in algorithmic complexity and explainability. To reflect real-world scenarios, models were trained on drugs approved before and within 2005 to predict the DICT risk of those approved thereafter. While we observed no clear association between prediction performance and model complexity, LR and XGBoost achieved the best results with DICTrank. Additionally, our significant-feature analyses with RF and XGBoost models provided novel insights into DICT mechanisms, revealing that drug properties associated with descriptors such as “structural and topological”, “polarizability”, and “electronegativity” contributed significantly to DICT. Moreover, we found that model performance varied by therapeutic category, suggesting the need to tailor models accordingly. In conclusion, our study demonstrated the robustness and reliability of DICTrank for cardiotoxicity prediction in humans using machine learning methods.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 4","pages":"647–655 647–655"},"PeriodicalIF":3.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diallyl Disulfide Reduces Ethyl Carbamate-Induced Cytotoxicity and Apoptosis in Intestinal and Hepatic Cells.","authors":"Caroline Andolfato Sanchez, Estefani Maria Treviso, Cecília Cristina de Souza Rocha, Lusânia Maria Greggi Antunes","doi":"10.1021/acs.chemrestox.4c00439","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00439","url":null,"abstract":"<p><p>Epidemiological studies indicate that lifestyle and dietary habits are associated with an increasing cancer incidence. Consuming fermented foods and alcoholic beverages and smoking can expose humans to ethyl carbamate (EC), a probable human carcinogen classified as group 2A by the International Agency for Research on Cancer (IARC). Increasing the intake of bioactive compounds can reduce EC-induced toxicity. Diallyl disulfide (DADS), found in garlic, may protect against damage induced by chemical agents and natural compounds. Here, the potential protective effect of DADS against EC was investigated by evaluating EC-induced cytotoxicity, DNA damage, apoptosis, and reactive oxygen species production in colorectal adenocarcinoma (Caco-2) and hepatocarcinoma (HepG2) cells. To this end, resazurin, comet, and annexin V-FITC staining assays and CM-H₂DCFDA markers were used to evaluate the effect on Caco-2 and HepG2 cells of protocols combining DADS (10-120 μM) and EC (80 mM). The protocols were as follows: (i) cells pretreated with DADS for 2 h and exposed to EC for 24 h; (ii) cells pretreated with DADS for 24 h and exposed to EC for 24 h; (iii) cells simultaneously exposed to DADS and EC for 24 h; (iv) cells exposed to EC for 24 h and treated with DADS for 2 h. EC induced cytotoxicity and apoptosis in Caco-2 and HepG2 cells and oxidative damage in Caco-2 cells. Combined exposure to DADS and EC for 24 h decreased EC-mediated cytotoxicity and apoptosis in both Caco-2 and HepG2 cells. These findings encourage further studies on the mechanisms of action of the combined DADS and EC.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA Methylation and Transcriptome Analysis Reveal Key Regulatory Pathways Related to Cadmium-Induced Liver Damage","authors":"Hao Huang,&nbsp;Guoliang Li,&nbsp;Sihui Guo,&nbsp;Kaile Li,&nbsp;Wei Li,&nbsp;Qinwen Zhou,&nbsp;Zhini He,&nbsp;Xingfen Yang*,&nbsp;Lili Liu* and Qinzhi Wei*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0053910.1021/acs.chemrestox.4c00539","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00539https://doi.org/10.1021/acs.chemrestox.4c00539","url":null,"abstract":"<p >Cadmium (Cd) is a prevalent environmental and industrial contaminant that causes significant damage to liver function. However, the role of m⁶A methylation─a critical epigenetic modification─in Cd-induced liver injury remains poorly understood. This study aimed to investigate the effects of m⁶A methylation in Cd-induced liver damage. A mouse model of Cd-induced liver injury was established, and exposure to CdCl₂ (20 mg/kg) for 90 days resulted in reduced m⁶A methylation levels. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-Seq), we characterized the m⁶A methylation profiles in both control and Cd-exposed groups. A total of 8355 unique m⁶A peaks and 1,101 unique m⁶A-modified genes were identified. Among these, 673 genes exhibited differential m⁶A methylated modifications, including 463 hyper-methylated and 210 hypo-methylated genes. Conjoint analysis of MeRIP-seq and RNA-Seq data unveiled genes that showed both differential methylation and expression. These genes were significantly enriched in the AGE-RAGE and PI3K-Akt signaling pathway. Through bioinformatics screening, five key genes (<i>Il-1β</i>, <i>Ccl2</i>, <i>Tlr2</i>, <i>Itgax</i>, and <i>Ccr2</i>) were identified, and expression validation indicated that <i>Itgax</i> and <i>Ccr2</i> may play pivotal roles in Cd-induced liver injury. Notably, elevated expression of methyltransferase-like 14 (METTL14) was observed in both in vivo and in vitro models. Inhibition of <i>Mettl14</i> can regulate Cd-induced liver inflammation through m⁶A-dependent regulation of <i>Ccr2</i> expression. Collectively, our findings highlight the crucial role of Mettl14 and Ccr2 in Cd-induced liver injury, providing novel insights into the epigenetic mechanisms underlying liver diseases and potential biomarkers for diagnosis and therapy.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 4","pages":"717–732 717–732"},"PeriodicalIF":3.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA Methylation and Transcriptome Analysis Reveal Key Regulatory Pathways Related to Cadmium-Induced Liver Damage.","authors":"Hao Huang, Guoliang Li, Sihui Guo, Kaile Li, Wei Li, Qinwen Zhou, Zhini He, Xingfen Yang, Lili Liu, Qinzhi Wei","doi":"10.1021/acs.chemrestox.4c00539","DOIUrl":"10.1021/acs.chemrestox.4c00539","url":null,"abstract":"<p><p>Cadmium (Cd) is a prevalent environmental and industrial contaminant that causes significant damage to liver function. However, the role of m⁶A methylation─a critical epigenetic modification─in Cd-induced liver injury remains poorly understood. This study aimed to investigate the effects of m⁶A methylation in Cd-induced liver damage. A mouse model of Cd-induced liver injury was established, and exposure to CdCl₂ (20 mg/kg) for 90 days resulted in reduced m⁶A methylation levels. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-Seq), we characterized the m⁶A methylation profiles in both control and Cd-exposed groups. A total of 8355 unique m⁶A peaks and 1,101 unique m⁶A-modified genes were identified. Among these, 673 genes exhibited differential m⁶A methylated modifications, including 463 hyper-methylated and 210 hypo-methylated genes. Conjoint analysis of MeRIP-seq and RNA-Seq data unveiled genes that showed both differential methylation and expression. These genes were significantly enriched in the AGE-RAGE and PI3K-Akt signaling pathway. Through bioinformatics screening, five key genes (<i>Il-1β</i>, <i>Ccl2</i>, <i>Tlr2</i>, <i>Itgax</i>, and <i>Ccr2</i>) were identified, and expression validation indicated that <i>Itgax</i> and <i>Ccr2</i> may play pivotal roles in Cd-induced liver injury. Notably, elevated expression of methyltransferase-like 14 (METTL14) was observed in both in vivo and in vitro models. Inhibition of <i>Mettl14</i> can regulate Cd-induced liver inflammation through m⁶A-dependent regulation of <i>Ccr2</i> expression. Collectively, our findings highlight the crucial role of Mettl14 and Ccr2 in Cd-induced liver injury, providing novel insights into the epigenetic mechanisms underlying liver diseases and potential biomarkers for diagnosis and therapy.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconjugation of Polychlorinated Biphenyl Sulfates to Hydroxylated PCBs by Anaerobically Cultured Mouse and Human Gut Microbiota","authors":"Xueshu Li,&nbsp;Joe J. Lim,&nbsp;Cayen Rong,&nbsp;Hans-Joachim Lehmler* and Julia Yue Cui*,&nbsp;","doi":"10.1021/acs.chemrestox.5c0001610.1021/acs.chemrestox.5c00016","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00016https://doi.org/10.1021/acs.chemrestox.5c00016","url":null,"abstract":"<p >The role of the gut microbiome in metabolizing polychlorinated biphenyls (PCBs), toxic environmental contaminants, and their metabolites remains unclear. This study used mouse and human microbiomes in anaerobic cultures to investigate the metabolism of PCB sulfate to hydroxylated PCBs (OH-PCBs). All microbiomes enzymatically hydrolyzed PCB sulfates. Higher chlorinated PCB sulfates were metabolized more readily. Male mouse microbiomes exhibited more PCB sulfate hydrolysis to OH-PCBs than female mouse microbiomes. Human microbiomes metabolized PCB sulfates to a more considerable extent than mouse microbiomes. They also showed variability in PCB sulfate metabolism, depending on the microbial communities. These findings suggest that the microbiome contributes to PCB metabolism.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 4","pages":"557–560 557–560"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrestox.5c00016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconjugation of Polychlorinated Biphenyl Sulfates to Hydroxylated PCBs by Anaerobically Cultured Mouse and Human Gut Microbiota.","authors":"Xueshu Li, Joe J Lim, Cayen Rong, Hans-Joachim Lehmler, Julia Yue Cui","doi":"10.1021/acs.chemrestox.5c00016","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00016","url":null,"abstract":"<p><p>The role of the gut microbiome in metabolizing polychlorinated biphenyls (PCBs), toxic environmental contaminants, and their metabolites remains unclear. This study used mouse and human microbiomes in anaerobic cultures to investigate the metabolism of PCB sulfate to hydroxylated PCBs (OH-PCBs). All microbiomes enzymatically hydrolyzed PCB sulfates. Higher chlorinated PCB sulfates were metabolized more readily. Male mouse microbiomes exhibited more PCB sulfate hydrolysis to OH-PCBs than female mouse microbiomes. Human microbiomes metabolized PCB sulfates to a more considerable extent than mouse microbiomes. They also showed variability in PCB sulfate metabolism, depending on the microbial communities. These findings suggest that the microbiome contributes to PCB metabolism.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}