Toxicology in Vitro最新文献_第7页

Inhibitory potential of phytochemicals on species-specific breast cancer resistance protein transport activity 植物化学物质对物种特异性乳腺癌抗性蛋白运输活性的抑制潜力。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2025-12-01 Epub Date: 2025-08-10 DOI: 10.1016/j.tiv.2025.106128

Lérica le Roux-Pullen , Jeroen J.M.W. van den Heuvel , Ilse R. Dubbelboer , Frans G.M. Russel , Ronette Gehring , Jan B. Koenderink

{"title":"Inhibitory potential of phytochemicals on species-specific breast cancer resistance protein transport activity","authors":"Lérica le Roux-Pullen , Jeroen J.M.W. van den Heuvel , Ilse R. Dubbelboer , Frans G.M. Russel , Ronette Gehring , Jan B. Koenderink","doi":"10.1016/j.tiv.2025.106128","DOIUrl":"10.1016/j.tiv.2025.106128","url":null,"abstract":"<div><div>The use of herbal alternatives in modern agriculture and healthcare offers a sustainable approach to animal and human health, but raises concerns about safety, particularly regarding phytochemical interactions at membrane transport proteins. Phytochemicals – bioactive compounds found in herbs - can influence the function of the breast cancer resistance protein (BCRP/ABCG2). BCRP is a key efflux transporter in mammals and in particularly abundant in the blood-milk-barrier of lactating animals, with the potential to affect milk quality and safety. This study investigates species-specific interactions of eight selected phytochemicals with BCRP orthologs in humans, cows, sheep and goats, using a transport assay with membrane vesicles derived from species-specific BCRP-overexpressing HEK293 cells. Five phytochemicals, namely apigenin, berberine, kaempferol, N-isobutyldodeca-2E4E8Z10E/<em>Z</em>-tetraenamide and quercetin inhibited BCRP-mediated transport of its prototypic substrate [<sup>3</sup>H]estrone sulfate by more than 30 % in all species. IC<sub>50</sub> values and, assuming competitive inhibition, Ki values were calculated for these compounds. Apigenin and kaempferol were the most potent inhibitors with Ki values <0.1 μM in all species, while N-isobutyldodeca-2E4E8Z10E/<em>Z</em>-tetraenamide was the weakest inhibitor (Ki > 30 μM). No significant interspecies differences in inhibitory potency were observed. Understanding the cross-species effects of bioactive compounds on BCRP activity is essential for predicting their broader biological impacts. Similar inhibition trends across species facilitate interspecies extrapolation and minimize the amount of animal studies needed to further investigate the effect of these phytochemicals on milk composition.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106128"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838549","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}

引用次数: 0

Lupeol-loaded PLGA particles conserve anti-topoisomerase activity and decrease the cytotoxicity of lupeol 负载lupeol的PLGA颗粒保持抗拓扑异构酶活性，降低lupeol的细胞毒性。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-12-01 Epub Date: 2025-07-15 DOI: 10.1016/j.tiv.2025.106107

Francisco Fabián Razura-Carmona , Mayra Herrera-Martínez , Jorge Alberto Sánchez-Burgos , Alejandro Pérez-Larios , Karina Janice Guadalupe Díaz-Reséndiz , Manuel Iván Girón-Pérez , Marco Vinicio Ramírez-Mares

{"title":"Lupeol-loaded PLGA particles conserve anti-topoisomerase activity and decrease the cytotoxicity of lupeol","authors":"Francisco Fabián Razura-Carmona , Mayra Herrera-Martínez , Jorge Alberto Sánchez-Burgos , Alejandro Pérez-Larios , Karina Janice Guadalupe Díaz-Reséndiz , Manuel Iván Girón-Pérez , Marco Vinicio Ramírez-Mares","doi":"10.1016/j.tiv.2025.106107","DOIUrl":"10.1016/j.tiv.2025.106107","url":null,"abstract":"<div><div>Lupeol (LP), a bioactive triterpene, has been extensively studied for its chemoprotective, anti-inflammatory, and anti-arthritic properties. To enhance its bioavailability, lupeol-loaded polylactic-<em>co</em>-glycolic acid (PLGA) nanoparticles, designated T<sub>LP</sub>14, were developed using the emulsification-evaporation method. These nanoparticles exhibited an average size of 339.8 nm, a polydispersity index (PdI) of 0.240, and an encapsulation efficiency of 38 %. In topoisomerase II inhibition assays, T<sub>LP</sub>14 retained activity comparable to that of lupeol free, indicating that encapsulation does not impair its biological function. <em>In vitro</em> cytotoxicity assays on BEAS-2 and HEPG2 cell lines demonstrated that concentrations above 1250 μg/mL of T<sub>LP</sub>14 induced minimal cytotoxic effects, suggesting low toxicity in non-tumor cells. Furthermore, <em>ex vivo</em> studies on peripheral blood mononuclear cells showed that a 1000 μg/mL concentration of free lupeol induced 28.01 % apoptosis, while the encapsulated formulation significantly reduced this adverse effect. These findings support the potential of T<sub>LP</sub>14 nanoparticles as an effective controlled-release system for lupeol, enhancing its safety profile while preserving its therapeutic activity.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106107"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661008","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}

引用次数: 0

Polystyrene nanoplastic co-exposed to BPA and BPS induces cytotoxicity, genotoxicity, and alters ROS production in HepG2 cells 聚苯乙烯纳米塑料共同暴露于BPA和BPS诱导细胞毒性，遗传毒性，并改变HepG2细胞的ROS产生

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-12-01 Epub Date: 2025-07-23 DOI: 10.1016/j.tiv.2025.106121

Cecilia Cristina de Souza Rocha , Caroline Andolfato Sanchez , Marília Cristina Oliveira Souza , Estéfani Maria Treviso , Gabriel Henrique Savietto , Paula Pícoli Devóz , Lucas Victor Pereira de Freitas , Lusânia Maria Greggi Antunes , Jonas Augusto Rizzato Paschoal , Fernando Barbosa Junior

{"title":"Polystyrene nanoplastic co-exposed to BPA and BPS induces cytotoxicity, genotoxicity, and alters ROS production in HepG2 cells","authors":"Cecilia Cristina de Souza Rocha , Caroline Andolfato Sanchez , Marília Cristina Oliveira Souza , Estéfani Maria Treviso , Gabriel Henrique Savietto , Paula Pícoli Devóz , Lucas Victor Pereira de Freitas , Lusânia Maria Greggi Antunes , Jonas Augusto Rizzato Paschoal , Fernando Barbosa Junior","doi":"10.1016/j.tiv.2025.106121","DOIUrl":"10.1016/j.tiv.2025.106121","url":null,"abstract":"<div><div>During plastic degradation, it is fragmented into micro and nanoplastic, which can adsorb contaminants from the environment, increasing the plastics´ toxicity. Bisphenol A is used in plastic production and can be an endocrine disruptor. Bisphenol S is an analog of bisphenol A and has been used as an alternative to “BPA-free” products. Therefore, this is the first research proposing to verify whether nanoplastics associated with bisphenol A or S can increase toxicity in HepG2 cells. Nanoplastics associated with bisphenols could alter the cell viability of HepG2 cells compared to the group treated with the nanoplastic alone and concerning the respective bisphenol. The co-exposure of nanoplastic to bisphenols A or S promoted cytotoxic and genotoxic damage in HepG2 cells, altering the reactive oxygen species production, increasing DNA strand breaks, and increasing apoptotic cells. Bisphenols A and S also showed cytotoxic and genotoxic effects in HepG2 cells. However, 8-OHdG was only detected in the group treated with the nanoplastic at the lowest concentration. This study highlights the cytotoxicity and genotoxicity of nanoplastics and bisphenols A and S, providing new insights into hepatocyte toxicity.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106121"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704468","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}

引用次数: 0

Beyond traditional toxicology: The transformative power of PBTK modeling 超越传统毒理学：PBTK建模的变革力量

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-12-01 Epub Date: 2025-07-18 DOI: 10.1016/j.tiv.2025.106111

Anagha Damre, Aniruddha Banerjee

{"title":"Beyond traditional toxicology: The transformative power of PBTK modeling","authors":"Anagha Damre, Aniruddha Banerjee","doi":"10.1016/j.tiv.2025.106111","DOIUrl":"10.1016/j.tiv.2025.106111","url":null,"abstract":"<div><div>Physiologically Based Toxicokinetic (PBTK) modeling has emerged as a crucial tool in toxicokinetics, enabling the quantitative assessment of chemical absorption, distribution, metabolism, and excretion (ADME) across various biological systems. Unlike traditional toxicokinetic approaches, PBTK models integrate physiological and biochemical parameters to allow for precise interspecies and dose extrapolations. This capability enhances their applicability in regulatory risk assessment for pharmaceuticals, industrial chemicals, food additives, cosmetics, and pesticides. High Throughput Toxicokinetics (HTTK) and in vitro-to-in vivo extrapolations (IVIVE) further improve the predictive power of PBTK models by utilizing large-scale experimental datasets and computational approaches. Additionally, these models facilitate route-to-route extrapolations, predicting systemic exposure across different administration routes such as oral, inhalation, and dermal pathways. PBTK modeling also enables the estimation of specific target tissue concentrations, cross-species extrapolations, and extrapolations to special populations, thereby improving human biological modeling. Furthermore, the integration of PBTK models in ecological risk assessment supports the evaluation of environmental chemical exposure effects on diverse species. As regulatory agencies increasingly adopt PBTK models for toxicity evaluations, their role in advancing data-driven risk assessment and reducing reliance on animal testing continues to grow. This review explores the application of PBTK modeling in toxicokinetics and its alignment with regulatory guidelines for risk assessment and interspecies extrapolation.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106111"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672141","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}

引用次数: 0

In vitro evaluation of antimicrobial food packaging: Assessing its inflammatory and sensitization potential 抗菌食品包装的体外评价：评估其炎症和致敏潜力

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-06-15 DOI: 10.1016/j.tiv.2025.106083

Franziska Trodtfeld, Cornelia Wiegand

{"title":"In vitro evaluation of antimicrobial food packaging: Assessing its inflammatory and sensitization potential","authors":"Franziska Trodtfeld, Cornelia Wiegand","doi":"10.1016/j.tiv.2025.106083","DOIUrl":"10.1016/j.tiv.2025.106083","url":null,"abstract":"<div><div>Skin sensitization is a key endpoint in chemical safety assessment for cosmetics and personal care products and is increasingly suggested for consideration in the evaluation of packaging materials, especially food packaging materials. Keratinocyte activation, involving oxidative stress, cytokine release, and the engagement of stress-related signaling pathways, represents an early and critical event in this process. In this study, we evaluated the responses of primary keratinocytes (PK), epidermis equivalents exposed to solutions (Epi-Sol), and coatings (Epi-Coat) to known skin sensitizers and antimicrobial agents included in food packaging.</div><div>Cytokine measurements (IL-1α, IL-6, IL-8, IL-18), gene expression profiling of stress and immune-related genes (<em>HMOX1, MMP10, DUSP1, HSP90AA1, ICAM1, IL4R, IL23A, IL33</em>), and histological analyses were performed. PK models exhibited the strongest and most diverse responses, with consistent <em>HMOX1</em> upregulation and robust inflammatory signaling. Epi-Sol models exhibited moderate responses, whereas Epi-Coat models showed lower reactivity, emphasizing the impact of both exposure method and model selection. Nanoparticles (Ag-NPs, ZnO-NPs) triggered exposure-dependent effects, with coatings limiting inflammatory signaling and tissue penetration. Histological changes confirmed barrier disruption and keratinocyte hyperproliferation in models exposed to stronger sensitizers.</div><div>Overall, these findings demonstrate that no single biomarker or model is sufficient for accurate safety assessment and support the use of multi-test, multi-endpoint evaluation strategies — particularly for emerging applications like food-contact materials — to ensure reliable hazard identification and material safety evaluation.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106083"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312903","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}

引用次数: 0

Dodecyldimethylamine oxide may induce lysosomal-associated cell death: Potential lipotoxicity 十二烷基二甲胺氧化物可能诱导溶酶体相关细胞死亡：潜在的脂肪毒性。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-06-24 DOI: 10.1016/j.tiv.2025.106102

Eun-Jung Park , Minseok Seo , Wonkyun Jung , Hyosun Choi , Ji Ae Lee

{"title":"Dodecyldimethylamine oxide may induce lysosomal-associated cell death: Potential lipotoxicity","authors":"Eun-Jung Park , Minseok Seo , Wonkyun Jung , Hyosun Choi , Ji Ae Lee","doi":"10.1016/j.tiv.2025.106102","DOIUrl":"10.1016/j.tiv.2025.106102","url":null,"abstract":"<div><div>Dodecyldimethylamine oxide (DDAO) is one of the most commonly used chemicals in household products, including spray types. We identified the potential toxicity mechanism using human bronchial epithelial cells. After 6 h of exposure, DDAO decreased cell viability (non-apoptotic cell death) and formed numerous small artificial vacuoles in the cytoplasm. Cellular impedance decreased rapidly following exposure to DDAO, and condensation of the inner mitochondrial membrane, an increased level of cytochrome C, and a decrease in ATP production and mitochondrial volume were observed in DDAO-treated cells, affecting the level of second messengers. Impaired intracellular components, including lamellar bodies, were also found within the mitochondria or vacuoles. While the secretion of chemotactic cytokines decreased, the levels of IL-6, IL-11, MMP-1, and MMP-3 increased. Furthermore, DDAO enhanced the expression of the LAMP-2 protein and notably increased the volume of acidic compartments. More importantly, the expression of lipid metabolism-related genes was most affected following DDAO treatment. Considering that the volume of acidic compartments decreased rapidly at a concentration of 40 μg/mL, we suggest that DDAO may induce lysosomal-associated cell death (possible lipotoxicity) through structural damage to the cell (mitochondria) membrane, and that lysosomal membrane proteins may contribute to protecting cells from DDAO-induced impacts.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106102"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509379","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}

引用次数: 0

Use of centromeric probe to identify micronuclei origin and its advantages in genetic toxicology studies 利用着丝粒探针鉴定微核起源及其在遗传毒理学研究中的优势

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-05-26 DOI: 10.1016/j.tiv.2025.106087

G. Tamizh Selvan , P. Venkatachalam

{"title":"Use of centromeric probe to identify micronuclei origin and its advantages in genetic toxicology studies","authors":"G. Tamizh Selvan , P. Venkatachalam","doi":"10.1016/j.tiv.2025.106087","DOIUrl":"10.1016/j.tiv.2025.106087","url":null,"abstract":"<div><div>Fluorescence <em>in situ</em> hybridization (FISH) and karyotyping have long been considered essential for chromosomal examination to analyse the stable chromosome aberrations such as translocations after exposure to genotoxic agents. To improve speed of chromosomal analysis in genetic toxicology investigations, we employed the cytokinesis-block micronucleus (CBMN) assay with human pan-centromeric probes, to measure chromosome segregation errors and to differentiate mechanism of action of genotoxic agents. Whole-blood collected from healthy volunteers were exposed to X-rays, bleomycin (BLM), Colchicine (COL) and Mitomycin-C (MMC), arrested at cytokinesis stage and processed for conventional giemsa staining and pan-centromeric FISH to analyse the composition of MN to differentiate between aneugen and clastogen effects. One-way ANOVA with Tukey's multiple comparison test exhibited a significant (<em>p</em> < 0.001) increase in the MN observed using giemsa stained and centromere FISH binucleated cells in all those genotoxic agents when compared to its unexposed lymphocytes cultures. The CBMN with centromere FISH, predominantly shows MNCN<sup>-ve</sup> cells in lymphocytes exposed to X-rays (67.4 % and 83.3 %), BLM (79.4 % and 79.2 %) and MMC (81.5 % and 73.2) while, COL treatment resulted in significantly (<em>p</em> < 0.05) higher MNCN<sup>+ve</sup> cells (79.6 % and 82.4 %) for the different concentrations of those agents. Centromere FISH enables to identify the origin of MN induced by different genotoxic agents. Thus, a significant development in genetic toxicology is heralded by the incorporation of centromeric probe in modern analytical workflows.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106087"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168142","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}

引用次数: 0

Toxicoproteomic study of fipronil in SH-SY5Y cells reveals induction of endoplasmic reticulum stress and necrotic cell death as neurodegenerative mechanisms 氟虫腈在SH-SY5Y细胞中的毒性蛋白质组学研究揭示了内质网应激和坏死细胞死亡是神经退行性机制

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-05-29 DOI: 10.1016/j.tiv.2025.106098

Theetat Ruangjaroon , N. Monique Paricharttanakul , Daranee Chokchaichamnankit , Chantragan Srisomsap , Kriengsak Lirdprapamongkol , Jisnuson Svasti

{"title":"Toxicoproteomic study of fipronil in SH-SY5Y cells reveals induction of endoplasmic reticulum stress and necrotic cell death as neurodegenerative mechanisms","authors":"Theetat Ruangjaroon , N. Monique Paricharttanakul , Daranee Chokchaichamnankit , Chantragan Srisomsap , Kriengsak Lirdprapamongkol , Jisnuson Svasti","doi":"10.1016/j.tiv.2025.106098","DOIUrl":"10.1016/j.tiv.2025.106098","url":null,"abstract":"<div><div>Exposure to pesticides has been considered as a risk factor for developing neurodegenerative diseases. The increasing use of fipronil, a phenylpyrazole insecticide, poses a risk to human health. This study aims to use toxicoproteomics for exploring neurodegenerative mechanism of fipronil in SH-SY5Y human neuroblastoma cells. In this study, fipronil at sub-cytotoxic and cytotoxic concentrations (43 and 78 μM) caused increases in superoxide level from 3 to 48 h after treatment, while intracellular glutathione level was decreased at 48 h. Neurite outgrowth of the cells was impaired by fipronil at both concentrations, while significant increase of cell death via apoptosis and necrosis modes were observed with fipronil at cytotoxic concentration. Pretreatment with antioxidant <em>N</em>-acetylcysteine (NAC) effectively relieved impairment of neurite outgrowth and induction of cell death by fipronil. Proteomic analysis showed that expression of proteins involving endoplasmic reticulum (ER) stress and unfolded protein responses were predominantly affected by fipronil. Immunoblotting confirmed the increased expression of ER stress markers, GRP78/BiP (78 kDa glucose-regulated protein/Binding immunoglobulin protein) and PDI (protein disulfide isomerase), in fipronil-treated cells. Improved understanding of the neurotoxic mechanism of fipronil may help in developing a strategy for reducing risk of neurodegenerative development from intense and prolonged use of fipronil.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106098"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178811","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}

引用次数: 0

Chronic exposure to palmitic acid-induced adipocyte hypertrophy and altered batokine gene expression in T37i brown adipocytes 慢性暴露于棕榈酸诱导的脂肪细胞肥大和T37i棕色脂肪细胞中细胞因子基因表达的改变。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-05-29 DOI: 10.1016/j.tiv.2025.106097

Khanyisani Ziqubu , Phiwayinkosi V. Dludla , Sithandiwe E. Mazibuko-Mbeje

{"title":"Chronic exposure to palmitic acid-induced adipocyte hypertrophy and altered batokine gene expression in T37i brown adipocytes","authors":"Khanyisani Ziqubu , Phiwayinkosi V. Dludla , Sithandiwe E. Mazibuko-Mbeje","doi":"10.1016/j.tiv.2025.106097","DOIUrl":"10.1016/j.tiv.2025.106097","url":null,"abstract":"<div><div>Enlargement of adipose tissue through hypertrophy is a key hallmark of obesity. Our previous study demonstrated that chronic obesity induces brown adipose tissue hypertrophy and altered batokine gene expression patterns <em>in vivo</em>. The present study further explored and verified the pathophysiological and molecular changes implicated in brown adipocyte hypertrophy by exposing T37i cells to 0.25, 0.5, 0.75, and 1 mM of palmitic acid for 48 h. The results showed that palmitic acid-induced intracellular lipid accumulation and lipolysis. Gene expression analysis demonstrated that palmitic acid downregulated genes responsible for glucose and lipid metabolism, such as <em>AdipoQ</em> and <em>PIk3r1</em>, while upregulating <em>Cpt1A</em>, a mitochondrial fatty acid transporter, and <em>Tnf-α</em>, a pro-inflammatory cytokine. Moreover, palmitic acid downregulated brown adipocyte transcriptional factors and thermogenic markers, including <em>Prdm16</em>, <em>Pparg</em>, <em>Cidea</em>, <em>Dio2</em>, <em>Sirt1,</em> and <em>Ucp1</em>. Gene expression of batokines involved in regulating substrate metabolism (<em>Fgf21</em>), angiogenesis (<em>Nrg4</em> and <em>VegfA</em>), and immune cell recruitment (<em>Metrnl</em>, <em>Gdf15,</em> and <em>Cxcl14</em>) were altered by palmitic acid. This data has demonstrated that palmitic acid contributes to the hypertrophy and whitening of brown adipocytes by inhibiting brown adipocyte differentiation and altering batokines expression patterns.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106097"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192530","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}

引用次数: 0

The protective mechanisms of glycyrrhizic acid for deoxynivalenol-induced toxicity in rabbit corneal stroma 甘草酸对脱氧雪腐镰刀醇致兔角膜基质毒性的保护机制。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-07-04 DOI: 10.1016/j.tiv.2025.106104

Chunlan Liang , Xuewei Xiong , Qi Shi , Qingqing Li , Guocheng Yu , Jingxiang Zhong , Lian Liu

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