Emanuel Kemmler, Margitta Worm, Robert Preissner, Priyanka Banerjee
{"title":"KNUTS-DB - a data-driven knowledge database for NUTS.","authors":"Emanuel Kemmler, Margitta Worm, Robert Preissner, Priyanka Banerjee","doi":"10.1080/15376516.2025.2496752","DOIUrl":"https://doi.org/10.1080/15376516.2025.2496752","url":null,"abstract":"<p><strong>Objectives: </strong>Databases specifying the nutrients and allergens present in multi-ingredient foods are required to explore the effect of food consumption on health outcomes accurately. The phytochemicals found in tree nuts have been associated with antioxidant, anti-inflammatory, antiproliferative, antiviral, chemo preventive and hypercholesterolaemic actions, all of which are known to affect the initiation and progression of several pathogenic processes. We have developed KNUTS-DB - a data-driven knowledge database for nuts - containing information on the chemical nutrients, molecular targets, pathways, disease associations, and clinically defined food allergen properties of peanuts and tree nuts.</p><p><strong>Methods: </strong>The database includes data sets associated with extremely rich and diverse metadata on almonds, cashew, pecan, walnut, pistachio, peanut and walnut. Additionally, the database allows users to perform pathway and GO-Term enrichment analysis for user-defined chemical nutrients. The results of the analysis are presented using heatmaps and network plots.</p><p><strong>Results: </strong>The database can be searched using options such as similarity search, interaction values, type of allergens, and specific nut types. KNUTS-DB offers researchers a unique platform to explore nuts' chemical composition and to investigate associations between nut composition and health outcomes - providing deeper insights into the molecular mechanisms.</p><p><strong>Conclusions: </strong>KNUTS-DB, the first of its kind, is freely available to all users via https://allergypred.charite.de/KNutsDB/ without any login or registration.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-8"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abbas Razmi, Enayatollah Seydi, Behnaz Ashtari, Ali Neshasteh-Riz, Parvaneh Naserzadeh
{"title":"New mechanistic approach of TiCN film-coated NiTi substrate toxicity: impairment in mitochondrial electron transfer in diabetic rat tooth gum cells.","authors":"Abbas Razmi, Enayatollah Seydi, Behnaz Ashtari, Ali Neshasteh-Riz, Parvaneh Naserzadeh","doi":"10.1080/15376516.2025.2479000","DOIUrl":"10.1080/15376516.2025.2479000","url":null,"abstract":"<p><p>In recent years, researchers have focused on using new materials for screws in bone jaw tissue replacement. However, concerns regarding the cytotoxicity and biocompatibility of these materials for cells remain a subject of ongoing discussion. In this study, a novel implant for bone jaw tissue regeneration was fabricated by depositing the titanium carbo-nitride (TiCN) film on NiTi shape memory alloy substrate using the Cathodic Arc Physical Vapor Deposition (CAPVD) technique. Our study emphasized positive cellular responses of TiCN-coated NiTi substrate on diabetic rat tooth gum cells for 1, 15, and 30 days. Initially, the evaluation focused on the characterization and distribution of NiTi alloy in tissues. Then, the levels of factors such as components of White Blood Cells (WBC), ATP, oxidative stress parameters, cytochrome c release and damage to the lysosomal membrane were evaluated in all groups. The results indicated that in the group of diabetic rats with TiCN-coated NiTi substrate, the level of oxidative stress parameters decreased. In addition, the cell viability, glutathione (GSH) intracellular and ATP increased and the rate of cytochrome c release, and damage to the lysosome membrane decreased. It can be concluded that the TiCN-coated NiTi screw is a promising material for bone jaw tissue replacement in diabetic patients due to its low cytotoxicity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"TGFBR2 as a prognostic marker and therapeutic target in benzo(a)pyrene-associated esophageal cancer: insights from multi-omics analysis.","authors":"Hongying Zhou, Xiaochun Lv, Yun Chen, Zhiquan Qin","doi":"10.1080/15376516.2025.2495930","DOIUrl":"https://doi.org/10.1080/15376516.2025.2495930","url":null,"abstract":"<p><strong>Background: </strong>Benzo(a)pyrene (BaP) is an environmental pollutant linked to several cancers, including esophageal cancer (ESCA). Understanding its impact on gene expression and associated molecular pathways in ESCA is crucial for developing targeted therapies.</p><p><strong>Methods: </strong>Using the TCGA-ESCA dataset, we identified differentially expressed genes (DEGs) related to BaP exposure. Enrichment analyses and protein-protein interaction (PPI) network construction were performed to explore the biological significance of these DEGs. Molecular docking studies assessed the interactions between BaP and core subnetwork genes. Survival analysis and immune cell infiltration analysis were conducted to evaluate the prognostic value of TGFBR2. Chemotherapy drug sensitivity was analyzed based on TGFBR2 expression levels.</p><p><strong>Results: </strong>We identified 5757 DEGs in ESCA, with 33 genes linked to both BaP exposure and ESCA. Enrichment analyses revealed significant pathways, including p53 signaling and apoptosis. Key genes (ACTB, CDKN2A, TGFBR2) were verified for their differential expression. Molecular docking demonstrated strong BaP binding to several core proteins. High TGFBR2 expression correlated with better survival, enhanced immune infiltration, and altered sensitivity to chemotherapeutic agents.</p><p><strong>Conclusion: </strong>Our study highlights the molecular mechanisms by which BaP influences ESCA, with TGFBR2 emerging as a potential prognostic marker and therapeutic target. These insights pave the way for personalized treatments in BaP-induced esophageal carcinogenesis.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ekramy M Elmorsy, Huda A Al Doghaither, Ayat B Al-Ghafari, Neven A Ebrahim, Saad Amer
{"title":"The flavonoid hyperoside attenuates the toxic effect of cisplatin on the human ovarian granulosa cells: <i>in vitro</i> model study.","authors":"Ekramy M Elmorsy, Huda A Al Doghaither, Ayat B Al-Ghafari, Neven A Ebrahim, Saad Amer","doi":"10.1080/15376516.2025.2491774","DOIUrl":"https://doi.org/10.1080/15376516.2025.2491774","url":null,"abstract":"<p><p>Premature ovarian insufficiency/failure is a well-known long-term risk of chemotherapy including CDDP in women. Granulosa cells (GCs) are an essential ovarian cell type that promotes oocyte growth and is crucial for ovarian reproductive function. Hyperoside (HYP) is a flavonoid known for its beneficial pharmacological properties, including anti-inflammatory and antiapoptotic effects. Hence the current work aimed to evaluate the potential cytoprotective impact of HYP on CDDP-induced cytotoxicity in a human ovarian GCs cell line model <i>via</i> a wide range of assays including MTT, hormones secretion, ATP and mitochondrial membrane potential, reactive oxygen species, lipid peroxidation as well as antioxidant enzymes, Caspases, and Akt kinase activities. Forty-eight-hour exposure to 5-10µM CDDP resulted in reduction of GCs viability in a dose-dependent manner. HYP (40 µM) was found to ameliorate this CDDP -induced effect on GCs viability. CDDP in a concentration-dependent way, dramatically reduced cellular ATP, mitochondrial activities, cellular progesterone, and estradiol secretion. It also increased oxidative stress markers, cytochrome c levels, caspase -3.-8.-9, and Bax/Bcl2 ratio with decreased Akt kinase activity and its coding genes expression. These cytotoxic effects of CDDP on the treated GCs, were mitigated to varying degrees by HYP (40 µM). In conclusion, CDDP-induced cytotoxic effects on GCs seem to be the possible underlying cellular and molecular mechanisms of CDDP-induced ovarian insufficiency/failure. The study also demonstrated the therapeutic potential of HYP in mitigating CDDP-induced ovarian injury. Further studies are warranted to investigate the potential benefit of HYP as an adjuvant to CDDP treatment protocols to avoid adverse ovarian effects.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A F Lehner, Justin Zyskowski, J P Buchweitz, D K Langlois
{"title":"Development of mass spectrometric methods for determination of desoxycorticosterone pivalate and its esterase product in canine serum.","authors":"A F Lehner, Justin Zyskowski, J P Buchweitz, D K Langlois","doi":"10.1080/15376516.2025.2489026","DOIUrl":"https://doi.org/10.1080/15376516.2025.2489026","url":null,"abstract":"<p><p>Hypoadrenocorticism is a serious condition in dogs that results from autoimmune adrenalitis and depletion of mineralocorticoids and glucocorticoids. Affected dogs respond well to glucocorticoid supplementation and treatment with the synthetic mineralocorticoid desoxycorticosterone pivalate (DOCP). DOCP injected once monthly resolves serum Na/K abnormalities and normalizes water balance, but therapy is expensive. Cost abatement involves prolongation of the 30-day dosage interval or decreasing the 2.2 mg/kg dosage. These approaches are not based on DOCP pharmacokinetics. A full assessment of the practicality of either approach would benefit from understanding drug pharmacokinetics, requiring measurement of DOCP and its esterase product desoxycorticosterone (DOC) in canine serum while avoiding toxic endpoints from overdosing. Mass spectrometric methods were developed including gas chromatography-tandem mass spectrometry of DOCP and DOC-methoxime trimethylsilyl derivatives, an approach sensitive to 2 ng/mL. Greater sensitivity was desired, so liquid chromatography-tandem mass spectrometry (LC-MS/MS) with ESI+ ionization was investigated. Supported liquid extraction was devised for serum with recoveries ∼100%. The LC-MS/MS method was validated for linearity, precision, accuracy and limits of detection (0.029 and 0.019 ng/mL for DOC and DOCP, respectively). A pilot experiment with DOCP-treated hypoadrenocorticism dogs over one-month revealed DOC baseline values as 0.183+/-0.090 ng/mL, which increased to the 1.0 - 2.2 ng/mL range. DOCP was not visible in any samples suggesting 100% conversion. Halving the dosage to 1.1 mg/kg still showed clear increases over the DOC baseline. MS fragmentation involved ring cleavages, dehydrations and double-charged fragments. The methodology was robust and suitable for studying DOC/DOCP pharmacokinetics in future studies of hypoadrenocorticism dogs.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guangyin Jia, Ruiji Zhang, Xinyi Zheng, Liujun Guo, Yan Zhao, Tingting Yan
{"title":"Mitochondrial toxic prediction of marine alga toxins using a predictive model based on feature coupling and ensemble learning algorithms.","authors":"Guangyin Jia, Ruiji Zhang, Xinyi Zheng, Liujun Guo, Yan Zhao, Tingting Yan","doi":"10.1080/15376516.2025.2484318","DOIUrl":"10.1080/15376516.2025.2484318","url":null,"abstract":"<p><p>Alga toxins have recently emerged as environmental risk factors to multiple human health issues. Mitochondrial toxicity is an essential element in the field of ecotoxicology, it is necessary to screen and manage mitochondrial toxicants from common alga toxins. To overcome the limitations of traditional animal and cell experiments, computational toxicology is increasingly emphasized. In this study, all the publicly available datasets were compiled to create the largest mitochondrial toxicity dataset to date, establishing a robust and high-performance QSAR screening model. The model couples and filters 12 molecular fingerprints and 318 descriptors as features, capturing more information about molecular structure and properties. By comparing 8 machine learning algorithms and using a weighted soft voting method to integrate the two optimal algorithms, we established 108 prediction models and identified the best ensemble learning model MACCS_LK for screening and defining its application domain. Additionally, the efficacy of MACCS fingerprints in representing mitochondrial toxicants was established, and a mechanistic analysis of the identified model based on the SHAP method and 11 structural alerts uncovered in this study was conducted, enhancing the interpretability of this model. This study highlights the key roles of lipophilic structures such as aromatic rings and long hydrocarbon chains and their related physicochemical properties in predicting toxicity outcomes. The mitochondrial toxicity of six algal toxins was predicted by employing this model, and the results indicating that two of them possess mitochondrial toxic effects. This model has high reliability and accuracy, making it applicable for predicting mitochondrial toxicity of more marine biotoxins.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-19"},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Green synthesized metal nanoparticles appear to meet expectations of low ecotoxicity: what about genotoxicity?","authors":"Fatma Okus, Deniz Yuzbasioglu, Fatma Unal","doi":"10.1080/15376516.2025.2487806","DOIUrl":"https://doi.org/10.1080/15376516.2025.2487806","url":null,"abstract":"<p><p>Advancements in technology and industry have made the use of nanomaterials indispensable. Due to concerns about the environmental damage caused by classical synthesis methods (Classical Synthesis, CS), the alternative 'Green Synthesis Method' (GS) has been developed, which aims to reduce toxicity by using environmentally friendly materials. This study examines whether nanoparticles synthesized through GS exhibit lower genotoxicity. To this end, research articles published between 2005 and 2025 on nanoparticle synthesis using the GS method were reviewed, and 551 studies were analyzed. The evaluation focused on gold, silver, platinum, copper, iron, and cobalt nanoparticles, which are widely used in various applications. The findings suggest that the GS method offers advantages in terms of genotoxicity. Additionally, this paper provides an in-depth analysis of how the GS method influences the properties of nanoparticles and explores the genotoxic mechanisms of nanoparticles synthesized through this approach.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of pumpkin and fermented whey on fecal microbiota profile against AFB1 and OTA exposure in Wistar rats.","authors":"Álvaro Lázaro, Pilar Gómez-Ramírez, Pilar Vila-Donat, Alessandra Cimbalo, Lara Manyes","doi":"10.1080/15376516.2025.2484636","DOIUrl":"10.1080/15376516.2025.2484636","url":null,"abstract":"<p><p>Mycotoxins perturb the gut microbiota performance. Bioactive compounds have been recently used as a new food strategy to diminish mycotoxins bioaccessibility and prevent their toxic effects on human and animal health. Male and female Wistar rats were exposed orally to twelve different diets containing aflatoxin B1 (AFB1) and/or ochratoxin A (OTA) with or without fermented whey (FW) and pumpkin (P) for 28 days. Fecal microbiota using 16S rRNA gene sequencing and subsequent metagenomics analysis were analyzed to study the effect of 28-day exposure through diet of contaminated and enriched feed. QIIME 2 microbiome analysis package (version 2024.5) was used to analyze the demultiplexed data. Mycotoxins-functional ingredients combination contributed more to microbial phylogenetic faith α-diversity rather than the functional ingredients alone, while the same combination reported a microbial α-diversity enhancement in comparison to the mycotoxins alone. Proteobacteria phylum was reduced in rat samples fed with contaminated diets (AFB1, OTA, and AFB1+OTA), while there was an increase-although not in all groups-when adding the functional ingredients. The main difference between the sexes was found in FW+AFB1+OTA group, with males (25%) showing higher % of <i>Proteobacteria</i> than females (1.86%). Phylogenetic diversity faith only focuses on microbial genetic (dis)similarity, not considering the biological function. <i>Morganella morganii</i>, a <i>Proteobacteria</i> found in some groups presents anticancer activity, but it is also related to inflammatory bowel disease and colorectal cancer. To sum up, both mycotoxins and functional ingredients trigger changes in the microbiota profile of Wistar rats in a sex-specific manner.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan Wang, Hui Sun, Kerong Hai, Ningkang Li, Yang Gu, Zengrui Ma
{"title":"Propofol alleviates traumatic brain injury through regulating Th17/Treg balance by activation of the AMPK/SIRT1 pathway.","authors":"Dan Wang, Hui Sun, Kerong Hai, Ningkang Li, Yang Gu, Zengrui Ma","doi":"10.1080/15376516.2025.2481893","DOIUrl":"https://doi.org/10.1080/15376516.2025.2481893","url":null,"abstract":"<p><p>Traumatic brain injury (TBI), a prevalent neurological disorder in clinical practice, is primarily induced by external trauma. Propofol has been reported to alleviate the symptoms associated with TBI. In this study, a TBI model was established in mice using the controlled cortical impact (CCI) method. After treatment with propofol and BML-275, neuronal damage in the TBI model was assessed through the modified Neurological Severity Score (mNSS), Hematoxylin and Eosin (HE) staining, and Nissl staining. To investigate the role of the AMPK/SIRT1 pathway in propofol-regulated TBI, AMPKα-silenced vectors and overexpressed SIRT1 vectors were transfected. Western blot was performed to evaluate the expression of proteins involved in the AMPK/SIRT1 pathway and pyroptosis markers. The regulatory impact of Th17/Treg balance was examined by detecting the key transcription factors RORγt and FOXP3 through immunofluorescent staining and RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to measure IL-17 and IL-10 concentrations. Results showed that propofol significantly reduced neuronal injury in the TBI model, an effect that was reversed by BML-275. Moreover, propofol mitigated pyroptosis by downregulating Caspase-1 and GSDMD-N expression post-TBI. Propofol inhibited Th17 differentiation while promoting Treg differentiation by modulating RORγt/FOXP3 and IL-17/IL-10 levels. Silencing AMPKα markedly diminished propofol's effects on Th17 and Treg differentiation, with these effects being reversed upon SIRT1 overexpression. Propofol suppressed neuronal pyroptosis through the regulation of Th17/Treg balance <i>via</i> activation of the AMPK/SIRT1 pathway. These findings suggest propofol exerts a protective effect against neuronal damage following TBI, potentially through the modulation of the Th17/Treg balance and AMPK/SIRT1 signaling pathway.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikola Vrzáčková, Petr Svoboda, Jana Dudová, Vojtěch Škop, Magdalena Melčová, Jaroslav Zelenka, Jana Pulkrabová, Tomáš Ruml
{"title":"Cellular mechanisms of medium-chain chlorinated paraffins toxicity: the effect of cellular lipid content.","authors":"Nikola Vrzáčková, Petr Svoboda, Jana Dudová, Vojtěch Škop, Magdalena Melčová, Jaroslav Zelenka, Jana Pulkrabová, Tomáš Ruml","doi":"10.1080/15376516.2025.2481909","DOIUrl":"https://doi.org/10.1080/15376516.2025.2481909","url":null,"abstract":"<p><p>Research on chlorinated paraffins (CPs) is growing, with accumulating evidence of CPs being present in biological matrices and animal tissues. However, their cellular-level impacts remain underexplored. This study investigates the effects of medium-chain CPs on adipose and liver cell models. The results show that CPs are more toxic at lower concentrations in 3T3-L1 preadipocytes than in adipocytes, suggesting that intracellular lipids may offer protection against these contaminants. However, neither simulated lipolysis in adipocytes nor lipogenesis in HepG2 hepatocytes revealed any lipid-dependent effects of CPs. CP exposure reduced <i>heme oxygenase 1</i> expression, indicating a biological response to these contaminants. In a coculture model of adipocytes and macrophages, CP exposure influenced cell signaling, with lipid-rich adipocytes modulating macrophage immune responses. Our results demonstrate that medium-chain CPs accumulation in lipid-rich tissues does not significantly affect their toxic effects. However, it may influence cell signaling within adipose tissue.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}