Journal of Applied Toxicology最新文献_第5页

Physiologically-based pharmacokinetic model of in vitro porcine ear skin permeation for drug delivery research 基于生理学的体外猪耳皮肤渗透药物动力学模型，用于给药研究。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-08-12 DOI: 10.1002/jat.4687

Laura Krumpholz, Sebastian Polak, Barbara Wiśniowska

{"title":"Physiologically-based pharmacokinetic model of in vitro porcine ear skin permeation for drug delivery research","authors":"Laura Krumpholz, Sebastian Polak, Barbara Wiśniowska","doi":"10.1002/jat.4687","DOIUrl":"10.1002/jat.4687","url":null,"abstract":"In silico techniques, such as physiologically based pharmacokinetic modeling (PBKP), are recently gaining importance. Computational methods in drug discovery and development and the generic drugs industry enhance research effectiveness by saving time and money and avoiding ethical issues. One key advantage is the ability to conduct toxicology studies without risking harm to living beings. This study aimed to repurpose the multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA) PBPK model for simulation permeation through porcine ear skin under in vitro conditions. The work was divided into four steps: (1) the development of a pig ear skin model based on a previously collected dataset; (2) testing the model's ability to discriminate permeation between pig ear, human abdomen, and human back skin; (3) development of a caffeine permeation model; and (4) testing the caffeine model's performance against in vitro generated data sourced from the scientific literature. Data from 31 manuscripts were used for the development of the pig skin model. Based on these data, values specific to pig skin were found for 22 parameters of the MPML MechDermA model. The model was able to discriminate permeation between pig and human skin. A caffeine model was developed and used to simulate seven experiments identified in the literature. The model's performance was assessed by comparing simulated to observed results. Based on a visual check, all simulations were considered acceptable, whereas three out of seven experiments met the twofold difference criterion. The variability of the experimental data was considered the biggest challenge for reliable model assessment.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 12","pages":"1936-1948"},"PeriodicalIF":2.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971197","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}

引用次数: 0

Taurine and enzymatically modified isoquercitrin protected against methotrexate-induced deteriorations in the conductivity and rhythmicity of the heart in rats: Antioxidant, anti-inflammatory, and histological architecture approach 牛磺酸和经酶制剂修饰的异槲皮素可防止甲氨蝶呤引起的大鼠心脏传导性和节律性恶化：抗氧化、抗炎和组织学结构方法。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-08-12 DOI: 10.1002/jat.4682

Marwa M. Mahmoud, Seham A. El-Batran, Rehab Hegazy, Wael M. El-Sayed

{"title":"Taurine and enzymatically modified isoquercitrin protected against methotrexate-induced deteriorations in the conductivity and rhythmicity of the heart in rats: Antioxidant, anti-inflammatory, and histological architecture approach","authors":"Marwa M. Mahmoud, Seham A. El-Batran, Rehab Hegazy, Wael M. El-Sayed","doi":"10.1002/jat.4682","DOIUrl":"10.1002/jat.4682","url":null,"abstract":"Cardiotoxicity is one of the most devastating complications of cancer treatment by methotrexate (MTX). The present study aimed to investigate the potential anti-cardiotoxic efficacy of taurine (Tau) and enzymatically modified isoquercitrin (EMIQ) alone or combined against MTX-induced cardiotoxicity in adult male rats. A total of 36 rats were randomly divided into six groups (six animals each): control, MTX (a single i.p. dose of 20 mg/kg), EMIQ + MTX (26 mg/kg of EMIQ, p.o. for 16 days), Tau + MTX (500 mg/kg of Tau, p.o. for 16 days), EMIQ + Tau + MTX at the same previous doses, and (EMIQ + Tau)½ + MTX. MTX reduced the percentage of body weight change, the expression of dihydrofolate reductase (DHFR) and folypolyglutamyl synthetase (FPGS), the cleaved tumor necrosis factor alpha (TNF-α) level in the cardiac tissue, and the elevated serum TNF-α level. MTX extensively deteriorated the electrocardiography (ECG), inducing tachycardia with shortening of the time intervals between successive heartbeats (R-R interval), associated with elongation of ventricular depolarization (QRS interval), and the corrected total time for ventricular de- and repolarization (QTc) duration. Treatment with MTX resulted in a significant reduction in atrial depolarization (P amplitude) and rapid repolarization (T amplitude) and a significant elevation in plateau phase (ST height). MTX treatment resulted in swelling of cardiomyocytes with extensive vacuolization of sarcoplasm with numerous variably sized vacuoles in addition to apoptotic cells. Tau and EMIQ protected against MTX-induced deteriorations in the conductivity and rhythmicity of the heart through antioxidative, anti-inflammatory, and antiapoptotic activities. Treatment with tau and EMIQ combined at high or low doses offered superior protection to the heart than using each agent alone.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 12","pages":"1924-1935"},"PeriodicalIF":2.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971198","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}

引用次数: 0

Non-chemical stresses do not strongly induce male offspring in Daphnia magna ascertained using the short-term juvenile hormone activity screening assay 利用短期幼体激素活性筛选试验确定，非化学胁迫不会强烈诱导大型蚤雄性后代的产生。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-08-12 DOI: 10.1002/jat.4678

Haruna Watanabe, Ryoko Abe, Norihisa Tatarazako, Hiroshi Yamamoto

{"title":"Non-chemical stresses do not strongly induce male offspring in Daphnia magna ascertained using the short-term juvenile hormone activity screening assay","authors":"Haruna Watanabe, Ryoko Abe, Norihisa Tatarazako, Hiroshi Yamamoto","doi":"10.1002/jat.4678","DOIUrl":"10.1002/jat.4678","url":null,"abstract":"Juvenile hormone (JH), together with ecdysone, regulates molting, metamorphosis, growth, and reproduction in arthropods. The effects of its analogs used as insecticides on nontarget species are of concern. Since JH and JH analogs (JHAs) induce male offspring in daphnids, which generally reproduce by parthenogenesis, short-term JH activity screening assay (JHASA) using the male offspring ratio as an endpoint has been developed as a detection method for JHA. However, the production of male offspring is also induced by environmental stresses such as temperature, short-day length, overcrowding, and food limitation. Thus, it is vital to prevent non-chemical stresses from inducing male offspring during the test to detect chemicals with potential JH activity accurately. Therefore, we investigated the effects of temperature (low and high), hardness, high density with low feeding, and day length on male production utilizing JHASA. Male offspring were not strongly induced by any stresses in JHASA, although the male ratios of 4–12% were observed in the preculture under high density (≥70 daphnid/L) and constant darkness. The Clone A strain was relatively more sensitive to high density and day length compared with the strain from National Institute for Environmental Studies (NIES). The selection of strains that rarely produce males under non-chemical stresses and finding the culturing conditions for each strain appropriate for not-inducing male offspring are recommended to control and prevent male offspring induction during JHASA.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 12","pages":"1914-1923"},"PeriodicalIF":2.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jat.4678","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico analysis of endocrine-disrupting potential of triclosan, bisphenol A, and their analogs and derivatives 三氯生、双酚 A 及其类似物和衍生物干扰内分泌潜能的硅学分析。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-08-11 DOI: 10.1002/jat.4685

Larisa Đurić, Maja Milanović, Jovana Drljača Lero, Nataša Milošević, Nataša Milić

{"title":"In silico analysis of endocrine-disrupting potential of triclosan, bisphenol A, and their analogs and derivatives","authors":"Larisa Đurić, Maja Milanović, Jovana Drljača Lero, Nataša Milošević, Nataša Milić","doi":"10.1002/jat.4685","DOIUrl":"10.1002/jat.4685","url":null,"abstract":"Owning to the increasing body of evidence about the ubiquitous exposure to endocrine disruptors (EDCs), particularly bisphenol A (BPA), and associated health effects, BPA has been gradually substituted with insufficiently tested structural analogs. The unmanaged excessive use of antimicrobial agents such as triclosan (TCS) during the COVID-19 outbreak has also raised concerns about its possible interferences with hormonal functions. The similarity of BPA and estradiol, as well as TCS and non-steroidal estrogens, imply that endocrine-disrupting properties of their analogs could be predicted based on the chemical structure. Hence, this study aimed to evaluate the endocrine-disrupting potential of BPA substitutes as well as TCS derivatives and degradation/biotransformation metabolites, in comparison to BPA and TCS based on their molecular properties, computational predictions of pharmacokinetics and binding affinities to nuclear receptors. Based on the obtained results several under-researched BPA analogs exhibited higher binding affinities for nuclear receptors than BPA. Notable analogs included compounds detected in receipts (DD-70, BTUM-70, TGSA, and BisOPP-A), along with a flame retardant, BDP. The possible health hazards linked to exposure to TCS and its mono-hydroxylated metabolites were also found. Further research is needed in order to elucidate the health impacts of these compounds and promote better regulation practices.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 12","pages":"1897-1913"},"PeriodicalIF":2.7,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916838","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}

引用次数: 0

Risk assessment of 2β,3β-19α-trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth 通过遗传毒性、新陈代谢和细胞生长，评估帝王蔷薇（蔷薇科）中的 2β,3β-19α-三羟基熊果酸在 HepG2/C3A 细胞中的风险。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-08-11 DOI: 10.1002/jat.4684

Bruna Oshiiwa, Aline Pereira da Silva, Greice Rafaele Alves, Valdir Cechinel Filho, Rivaldo Niero, Isabel O'Neill de Mascarenhas Gaivão, Liana Martins de Oliveira, Luan Vitor Alves de Lima, Mário Sérgio Mantovani, Edson Luis Maistro

{"title":"Risk assessment of 2β,3β-19α-trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth","authors":"Bruna Oshiiwa, Aline Pereira da Silva, Greice Rafaele Alves, Valdir Cechinel Filho, Rivaldo Niero, Isabel O'Neill de Mascarenhas Gaivão, Liana Martins de Oliveira, Luan Vitor Alves de Lima, Mário Sérgio Mantovani, Edson Luis Maistro","doi":"10.1002/jat.4684","DOIUrl":"10.1002/jat.4684","url":null,"abstract":"Rubus imperialis (Rosaceae) is a Brazilian medicinal plant that already exhibited therapeutical perspectives. However, previous studies revealed cellular and/or genetic toxicity of extracts from aerial parts of this plant, as well as other species of the Rubus genus. Being 2β,3β-19α-trihydroxyursolic acid (2B) one of the major compounds of this plant, with proven pharmacological effect, it is important to investigate the biosafety of this isolated compound. Therefore, in the present study, (2B) was tested by several cytogenotoxic endpoints up to 20 μg/ml in human hepatoma HepG2/C3A cells. The test compound did not produce any decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT-qPCR analysis revealed the downregulation of CYP3A4 (metabolism), M-TOR (cell death), and CDKN1A (cell cycle) genes. Under the experimental conditions used, the 2B compound did not show cytogenotoxic activity after a single exposure to HepG2/C3A human cells.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 12","pages":"1886-1896"},"PeriodicalIF":2.7,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916839","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}

引用次数: 0

90-day oral toxicity study in rats of a protein-rich powder derived from Xanthobacter sp. SoF1 从黄杆菌 SoF1 提取的富含蛋白质的粉末对大鼠进行的 90 天口服毒性研究。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-08-04 DOI: 10.1002/jat.4663

Bean Choi, Róbert Glávits, Timothy S. Murbach, John R. Endres, Gábor Hirka, Ilona Pasics Szakonyiné

引用次数: 0

The dimer effect: A refinement approach towards skin sensitization assessment in-chemico using Amino acid Derivative Reactivity Assay 二聚体效应：使用氨基酸衍生物反应性测定法进行皮肤过敏化学评估的改进方法。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-08-02 DOI: 10.1002/jat.4681

Ratnadeep Paul Choudhury, Akanksha Singh, Eldho Mathai, DGS Sudhakar, Fleur Tourneix, Nathalie Alépée, Francoise Gautier

{"title":"The dimer effect: A refinement approach towards skin sensitization assessment in-chemico using Amino acid Derivative Reactivity Assay","authors":"Ratnadeep Paul Choudhury, Akanksha Singh, Eldho Mathai, DGS Sudhakar, Fleur Tourneix, Nathalie Alépée, Francoise Gautier","doi":"10.1002/jat.4681","DOIUrl":"10.1002/jat.4681","url":null,"abstract":"Skin sensitization is a key endpoint for safety assessment, especially for cosmetics and personal care products. The adverse outcome pathway for skin sensitization and the chemical and biological events driving the induction of human skin sensitization are now well understood. Several non-animal test methods have been developed to predict sensitizer potential by measuring the impact of chemical sensitizers on these key events. In this work, we have focused on Key Event 1 (the molecular initiating step), which is based on formation of a covalent adduct between skin sensitizers and endogenous proteins and/or peptides in the skin. There exists three in-chemico assays approved by the Organization for Economic Co-operation and Development—(1) Direct Peptide Reactivity Assay (DPRA), (2) Amino Acid Derivative Reactivity Assay (ADRA), and (3) Kinetic Direct Peptide Reactivity Assay (kDPRA) to quantify peptide/amino acid derivative depletion after incubation with test chemicals. However, overestimated depletion of the cysteine-based peptide/amino acid derivatives is known in such assays because of the dimerization of the thiol group. In this present work, we report the synthesis and structural confirmation of the dimer of N-(2-[1-naphthyl]acetyl)-L-cysteine (NAC) from the ADRA assay to allow simultaneous determination of (a) peptide depletion by quantifying NAC monomer and (b) peptide dimerization by quantifying NAC dimer thereby eliminating the overestimation. We present a case study with three chemicals to demonstrate the importance of this approach. Thus, this simultaneous assay gives a more informed view of the peptide reactivity of chemicals to better identify skin sensitizers.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 11","pages":"1804-1815"},"PeriodicalIF":2.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878768","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}

引用次数: 0

Melatonin intervention to prevent nanomaterial exposure-induced damages: A systematic review and meta-analysis of in vitro and in vivo studies. 干预褪黑激素以预防纳米材料暴露引起的损害：体外和体内研究的系统回顾和荟萃分析。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-08-01 DOI: 10.1002/jat.4676

Xuejiao Wang, Yang Zhou, Dongli Xie, Fei Yin, Yunxia Liang, Xiaogang Luo

{"title":"Melatonin intervention to prevent nanomaterial exposure-induced damages: A systematic review and meta-analysis of in vitro and in vivo studies.","authors":"Xuejiao Wang, Yang Zhou, Dongli Xie, Fei Yin, Yunxia Liang, Xiaogang Luo","doi":"10.1002/jat.4676","DOIUrl":"https://doi.org/10.1002/jat.4676","url":null,"abstract":"Given its antioxidant, anti-inflammatory, and antiapoptotic properties, melatonin (MEL), a health-caring food to improve sleep disorders, is hypothesized to protect against nanomaterial exposure-induced toxicity. However, the conclusion derived from different studies seemed inconsistent. A meta-analysis of all available preclinical studies was performed to examine the effects of MEL on nanomaterial-induced damages. Eighteen relevant studies were retrieved through searching five electronic databases up to December 2023. The meta-analysis showed that relative to control, MEL treatment significantly increased cell viability (standardized mean difference [SMD = 1.27]) and alleviated liver function (lowered AST [SMD = -3.89] and ALT [SMD = -5.89]), bone formation (enhanced BV/TV [SMD = 4.13] and lessened eroded bone surface [SMD = -5.40]), and brain nerve (inhibition of AChE activity [SMD = -3.60]) damages in animals. The protective mechanisms of MEL against damages caused by nanomaterial exposure were associated with its antiapoptotic (decreased Bax/Bcl-2 ratio [SMD = -4.50] and caspase-3 levels [dose <100 μM: SMD = -3.66]), antioxidant (decreased MDA [in vitro: SMD = -2.84; in vivo: SMD = -4.27]), and anti-inflammatory (downregulated TNF-α [in vitro: SMD = -5.41; in vivo: SMD = -3.21] and IL-6 [in vitro: SMD = -5.90; in vivo: SMD = -2.81]) capabilities. In conclusion, our study suggests that MEL should be supplemented to prevent damages in populations exposed to nanomaterials.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874888","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}

引用次数: 0

Influences of TiO2 nanoparticle and fipronil co-exposure on metabolite profiles in mouse intestines TiO2纳米粒子和氟虫腈共同暴露对小鼠肠道代谢物特征的影响

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-07-29 DOI: 10.1002/jat.4680

Canyang Wang, Zhengzheng Zhou, Yayu He, Juan Li, Yi Cao

{"title":"Influences of TiO2 nanoparticle and fipronil co-exposure on metabolite profiles in mouse intestines","authors":"Canyang Wang, Zhengzheng Zhou, Yayu He, Juan Li, Yi Cao","doi":"10.1002/jat.4680","DOIUrl":"10.1002/jat.4680","url":null,"abstract":"Food contaminates, such as insecticide, may influence the toxicity of nanoparticles (NPs) to intestine. The present study investigated the combined toxicity of TiO2 NPs and fipronil to male mouse intestine. Juvenile mice (8 weeks) were orally exposed to 5.74 mg/kg TiO2 NPs, 2.5 mg/kg fipronil, or both, once a day, for 5 days. We found that both TiO2 NPs and fipronil induced some pathological changes in intestines, accompanying with defective autophagy, but these effects were not obviously enhanced after TiO2 NP and fipronil co-exposure. Fipronil promoted Ti accumulation but induced minimal impact on other trace elements in TiO2 NP-exposed intestines. Metabolomics data revealed that the exposure altered metabolite profiles in mouse intestines, and two KEGG pathways, namely, ascorbate and aldarate metabolism (mmu00053) and glutathione metabolism (mmu00480), were only statistically significantly changed after TiO2 NP and fipronil co-exposure. Five metabolites, including 2-deoxy-D-erythro-pentofuranose 5-phosphate, 5alpha-cholestanol, beta-D-glucopyranuronic acid, elaidic acid, and isopentadecanoic acid, and maltotriose, were more significantly up-regulated after the co-exposure, whereas trisaccharide and xylonolactone were only significantly down-regulated by the co-exposure. We concluded that fipronil had minimal impact to enhance the toxicity of TiO2 NPs to mouse intestines but altered metabolite profiles.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 11","pages":"1793-1803"},"PeriodicalIF":2.7,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792535","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}

引用次数: 0

Endocrine disruption of adipose physiology: Screening in SGBS cells 内分泌对脂肪生理的干扰：在 SGBS 细胞中进行筛选。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-07-23 DOI: 10.1002/jat.4679

Jan Kucera, Zuzana Chalupova, Martin Wabitsch, Julie Bienertova-Vasku

{"title":"Endocrine disruption of adipose physiology: Screening in SGBS cells","authors":"Jan Kucera, Zuzana Chalupova, Martin Wabitsch, Julie Bienertova-Vasku","doi":"10.1002/jat.4679","DOIUrl":"10.1002/jat.4679","url":null,"abstract":"The increasing use of industrial chemicals has raised concerns regarding exposure to endocrine-disrupting chemicals (EDCs), which interfere with developmental, reproductive and metabolic processes. Of particular concern is their interaction with adipose tissue, a vital component of the endocrine system regulating metabolic and hormonal functions. The SGBS (Simpson Golabi Behmel Syndrome) cell line, a well-established human-relevant model for adipocyte research, closely mimics native adipocytes' properties. It responds to hormonal stimuli, undergoes adipogenesis and has been successfully used to study the impact of EDCs on adipose biology. In this study, we screened human exposure-relevant doses of various EDCs on the SGBS cell line to investigate their effects on viability, lipid accumulation and adipogenesis-related protein expression. Submicromolar doses were generally well tolerated; however, at higher doses, EDCs compromised cell viability, with cadmium chloride (CdCl2) showing the most pronounced effects. Intracellular lipid levels remained unaffected by EDCs, except for tributyltin (TBT), used as a positive control, which induced a significant increase. Analysis of adipogenesis-related protein expression revealed several effects, including downregulation of fatty acid-binding protein 4 (FABP4) by dibutyl phthalate, upregulation by CdCl2 and downregulation of perilipin 1 and FABP4 by perfluorooctanoic acid. Additionally, TBT induced dose-dependent upregulation of C/EBPα, perilipin 1 and FABP4 protein expression. These findings underscore the importance of employing appropriate models to study EDC-adipocyte interactions. Conclusions from this research could guide strategies to reduce the negative impacts of EDC exposure on adipose tissue.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 11","pages":"1784-1792"},"PeriodicalIF":2.7,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jat.4679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0