Toxicology in Vitro最新文献

{"title":"Reference chemical database for the development and validation of in vitro alternatives to skin irritation and comparison of the performance of RhE models","authors":"Nam-Hee Kang,&nbsp;Min Kyung Hyun,&nbsp;Seo Young Bang","doi":"10.1016/j.tiv.2024.105851","DOIUrl":"10.1016/j.tiv.2024.105851","url":null,"abstract":"<div><p>After EU ban on animal testing for cosmetics in 2013, there has been an increasing global interest in alternatives test methods. To development for alternatives test method, we need to get the toxic data about <em>in vitro</em> and <em>in vivo</em> of chemicals. However, database sometimes provide limited <em>in vivo</em> and <em>in vitro</em> data on chemicals. Further, the data generated using the OECD TG439 (<em>in vitro</em> skin irritation) are scattered in difference databases, and it is not easy to navigate through them. Therefore, we complied ‘Reference Chemical Database System for Skin Irritation Alternative Test (RCDS-Skin Irritation)’ to allow easy, one-stop access to test chemical information. We established the systematic RCDS-Skin Irritation by collecting physiochemical properties, CAS number, human data, and <em>in vivo</em> (OECD TG404) data from overseas chemicals database including European Chemicals Agency (ECHA) <em>etc.</em>, and <em>in vitro</em> data using Reconstructed human Epidermis (RhE) (OECD TG439). As a result, we developed the RCDS-Skin Irritation that contains information on 149 chemicals including the data we generated by performing tests using EpiDerm™ SIT, SkinEthic™ RHE and KeraSkin™ SIT.</p><p>Therefore, the RCDS-Skin Irritation established based on our study will provide insight for safety assessment of chemicals and for development of alternative test methods.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"98 ","pages":"Article 105851"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094280","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":"In vitro inhibitory effects of selumetinib on activity of human UDP-glucuronosyltransferases and prediction of in vivo drug-drug interactions","authors":"Hang Yin,&nbsp;Xin Lv,&nbsp;Zhen Wang,&nbsp;Shichao Xiao,&nbsp;Jiaqi Liang,&nbsp;Jie Sun,&nbsp;Lili Jiang,&nbsp;Yong Liu","doi":"10.1016/j.tiv.2024.105863","DOIUrl":"10.1016/j.tiv.2024.105863","url":null,"abstract":"<div><p>Selumetinib is an oral, effective, and selective tyrosine kinase inhibitor targeting mitogen-activated protein kinase 1 and 2 (MEK1/2), which is clinically active in multiple tumor types, such as neurofibromatosis type 1 (NF1), melanoma, gliomas and non-small cell lung cancer (NSCLC). The purpose of this article was to assess the effects of selumetinib on the activities of twelve human UDP-glucosyltransferases (UGTs) including UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15, and 2B17, and its potential for inducing clinical drug-drug interactions (DDIs). The results demonstrated that selumetinib potently inhibited the activity of UGT2B7 through the mechanism of mixed inhibition with the inhibition constant value of 5.79 ± 0.65 μM. Furthermore, the plasma concentration of UGT2B7 substrate as the co-administered drug was predicted to be increased by at least 84 % when patients took selumetinib 75 mg twice daily, suggesting a high potential to induce clinical DDIs. Selumetinib exhibited weak inhibitory effects on other human UGTs and was unlikely to trigger off UGTs-mediated DDIs except for UGT2B7. Therefore, the combination of selumetinib with the substrate drug of UGT2B7 requires additional attention to avoid adverse events in clinical treatment.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105863"},"PeriodicalIF":3.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187026","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":"Cyclopenta[b]indoles as novel antimicrotubule agents with antileukemia activity","authors":"Hugo Passos Vicari ,&nbsp;Ralph da Costa Gomes ,&nbsp;Keli Lima ,&nbsp;Nicolas de Oliveira Rossini ,&nbsp;Manoel Trindade Rodrigues Junior ,&nbsp;Lívia Bassani Lins de Miranda ,&nbsp;Marcio Vinicius Bertacini Dias ,&nbsp;Leticia Veras Costa-Lotufo ,&nbsp;Fernando Coelho ,&nbsp;João Agostinho Machado-Neto","doi":"10.1016/j.tiv.2024.105856","DOIUrl":"10.1016/j.tiv.2024.105856","url":null,"abstract":"<div><p>Acute leukemias present therapeutic challenges despite advances in treatments. Microtubule inhibitors have played a pivotal role in cancer therapy, inspiring exploration into novel compounds like C2E1 from the cyclopenta[<em>b</em>]indole class. In the present study, we investigated C2E1's potential as a therapeutic agent for acute leukemia at molecular, cellular, and genetic levels. C2E1 demonstrated tubulin depolarization activity, significantly reducing leukemia cell viability. Its impact involved multifaceted mechanisms: inducing apoptosis, arrest of cell cycle progression, and inhibition of clonogenicity and migration in leukemia cells. At a molecular level, C2E1 triggered DNA damage, antiproliferative, and apoptosis markers and altered gene expression related to cytoskeletal regulation, disrupting essential cellular processes crucial for leukemia cell survival and proliferation. These findings highlight C2E1's promise as a potential candidate for novel anti-cancer therapies. Notably, its distinct mode of action from conventional microtubule-targeting drugs suggests the potential to bypass common resistance mechanisms encountered with existing treatments. In summary, C2E1 emerges as a compelling compound with diverse effects on leukemia cells, showcasing promising antineoplastic properties. Its ability to disrupt critical cellular functions selective to leukemia cells positions it as a candidate for future therapeutic development.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105856"},"PeriodicalIF":3.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184974","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":"The microRNA miR-152 can mitigate and prevent the toxic effect of benzene on porcine ovarian cells","authors":"Alexander V. Sirotkin ,&nbsp;Zuzana Fabová ,&nbsp;Barbora Loncová ,&nbsp;Kristína Popovičová ,&nbsp;Miroslav Bauer ,&nbsp;Maroua Jalouli ,&nbsp;Abdel Halim Harrath","doi":"10.1016/j.tiv.2024.105855","DOIUrl":"10.1016/j.tiv.2024.105855","url":null,"abstract":"<div><p>Epigenetic methods to prevent the reproductive toxicity of oil-related environmental contaminants are currently unavailable. The present study aimed to examine the ability of the microRNA miR-152 to mitigate the effects of benzene on ovarian cells. Porcine ovarian granulosa cells transfected or not transfected with miR-152 mimics were cultured with or without benzene (0, 10 and 100 ng/ml). The expression of miR-152; viability; proliferation (cell proliferation and expression of mRNAs and accumulation of PCNA and cyclin B1); apoptosis (expression of mRNAs and accumulation of bax and caspase 3; and the proportion of cells with fragmented DNA); and release of progesterone, estradiol and IGF-I were analyzed via RT–qPCR; the Trypan blue exclusion test; quantitative immunocytochemistry; BrdU; XTT; TUNEL assays; and ELISA.</p><p>Administration of benzene promoted the expression of apoptosis markers and reduced cell viability, all measured markers of proliferation, the release of steroid hormones and IGF-I. Overexpression of miR-152 was associated with increased cell viability, proliferation, progesterone and IGF-I release and reduced apoptosis and estradiol output. Moreover, miR-152 mitigated or prevented the effects of benzene on all the measured parameters in addition to estradiol release.</p><p>The present observations suggest the toxic effect of benzene and the stimulatory influence of miR-152 on ovarian cell functions. Moreover, this is the first demonstration of the ability of miRNAs to mitigate and prevent the reproductive toxicity of benzene.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105855"},"PeriodicalIF":3.2,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181383","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":"Bayesian analysis of physiologically based toxicokinetic (PBTK) modeling for pentachlorophenol exposure in pregnant women","authors":"Chunfeng Wu ,&nbsp;Yajiao Tan ,&nbsp;Xiaoyi Wei ,&nbsp;Xun Li ,&nbsp;Sifei Sun ,&nbsp;Bing Lyu ,&nbsp;Zhen Shen ,&nbsp;Xiao Wei ,&nbsp;Shuo Xiao ,&nbsp;Yuanyuan Ruan ,&nbsp;Jun Yu ,&nbsp;Gengsheng He ,&nbsp;Weiwei Zheng ,&nbsp;Jingguang Li","doi":"10.1016/j.tiv.2024.105853","DOIUrl":"10.1016/j.tiv.2024.105853","url":null,"abstract":"<div><p>Pentachlorophenol (PCP) is a persistent organic compound that is widely present in the environment. The estimation of internal exposure levels for a given external exposure using toxicokinetic models is key to the human health risk assessment of PCP. The present study developed a physiologically based multicompartmental pharmacokinetic (PBTK) model to describe and predict the behavior of pentachlorophenol (PCP) in an organism. The model consists of stomach, intestines, adipose tissue, kidneys and fast- and poorly perfused tissues that are interconnected via blood circulation. We constructed a PBTK model of PCP in rats and extrapolated it to human dietary PCP exposure. The toxicokinetic data of PCP in human tissues and excreta were obtained from the published literature. Based on the collected PCP dietary survey and internal exposure data of pregnant women in Shanghai, Bayesian statistical analysis was performed for the model using Markov chain Monte Carlo (MCMC) simulation. The posterior distributions of the sensitive parameters were estimated, and the model was parameter optimized and validated using the pregnant women's test dataset. The results showed that the root mean square error (RMSE) improved 37.3% compared to the original model, and a systematic literature search revealed that the optimized model achieved acceptable prediction results for other datasets in China. A PCP metabolism model based on the exposure characteristics of pregnant women in China was constructed in the present study. The model provides a theoretical basis for the study of PCP toxicity and risk assessment.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105853"},"PeriodicalIF":3.2,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162146","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":"Lack of cytotoxic and genotoxic effects of mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium despite cellular uptake in cancerous and noncancerous lung cells","authors":"Malgorzata Sikorska ,&nbsp;Monika Ruzycka-Ayoush ,&nbsp;Ivan Rios-Mondragon ,&nbsp;Eleonora Marta Longhin ,&nbsp;Sylwia Meczynska-Wielgosz ,&nbsp;Maria Wojewodzka ,&nbsp;Agata Kowalczyk ,&nbsp;Artur Kasprzak ,&nbsp;Julita Nowakowska ,&nbsp;Kamil Sobczak ,&nbsp;Magdalena Muszynska ,&nbsp;Mihaela Roxana Cimpan ,&nbsp;Elise Runden-Pran ,&nbsp;Sergey Shaposhnikov ,&nbsp;Marcin Kruszewski ,&nbsp;Maria Dusinska ,&nbsp;Anna M. Nowicka ,&nbsp;Ireneusz P. Grudzinski","doi":"10.1016/j.tiv.2024.105850","DOIUrl":"10.1016/j.tiv.2024.105850","url":null,"abstract":"<div><p>Cytotoxic and genotoxic effects of novel mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium (Mg_0.1-γ-Fe₂O₃(mPEG-silane)_0.5) have been investigated on human adenocarcinomic alveolar basal epithelial (A549) and human normal bronchial epithelial (BEAS-2B) cells. In the studies several molecular and cellular targets addressing to cell membrane, cytoplasm organelles and nucleus components were served as toxicological endpoints. The as-synthesized nanoparticles were found to be stable in the cell culture media and were examined for different concentration and exposure times. No cytotoxicity of the tested nanoparticles was found although these nanoparticles slightly increased reactive oxygen species in both cell types studied. Mg_0.1-γ-Fe₂O₃(mPEG-silane)_0.5 nanoparticles did not produce any DNA strand breaks and oxidative DNA damages in A549 and BEAS-2B cells. Different concentration of Mg_0.1-γ-Fe₂O₃(mPEG-silane)_0.5 nanoparticles and different incubation time did not affect cell migration. The lung cancer cells' uptake of the nanoparticles was more effective than in normal lung cells. Altogether, the results evidence that mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium do not elucidate any deleterious effects on human normal and cancerous lung cells despite cellular uptake of these nanoparticles. Therefore, it seems reasonable to conclude that these novel biocompatible nanoparticles are promising candidates for further development towards medical applications.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105850"},"PeriodicalIF":3.2,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159205","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":"Schisandrin B protect inner hair cells from cisplatin by inhibiting celluar oxidative stress and apoptosis","authors":"Yao Li ,&nbsp;Zhenzhen Liu ,&nbsp;Jun Chen ,&nbsp;Renfeng Wang,&nbsp;Xiaogang An,&nbsp;Chaoyong Tian,&nbsp;Han Yang,&nbsp;Dingjun Zha","doi":"10.1016/j.tiv.2024.105852","DOIUrl":"10.1016/j.tiv.2024.105852","url":null,"abstract":"<div><p>Cisplatin is an effective chemotherapeutic agent; however, ototoxicity is one of its negative effects that greatly limits the use of cisplatin in clinical settings. Previous research has shown that the most important process cisplatin damage to inner ear cells, such as hair cells (HCs), is the excessive production and accumulation of ROS. Schisandrin B (SchB), is a low-toxicity, inexpensive, naturally occurring antioxidant with a variety of pharmacological effects. Therefore, the potential antioxidant effects of SchB may be useful for cisplatin ototoxicity treatment. In this study, the effects of SchB on cochlear hair cell viability, ROS levels, and expression of apoptosis-related molecules were evaluated by CCK-8, immunofluorescence, flow cytometry, and qRT-PCR, as well as auditory brainstem response (ABR) and dysmorphic product otoacoustic emission (DPOAE) tests to assess the effects on inner ear function. The results showed that SchB treatment increased cell survival, prevented apoptosis, and reduced cisplatin-induced ROS formation. SchB treatment reduced the loss of cochlear HCs caused by cisplatin in exosome culture. In addition, SchB treatment attenuated cisplatin-induced hearing loss and HC loss in mice. This study demonstrates the ability of SchB to inhibit cochlear hair cell apoptosis and ROS generation and shows its potential therapeutic effect on cisplatin ototoxicity.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105852"},"PeriodicalIF":3.2,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094446","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":"Antifungal climbazole alters androgenic pathways in mammalian cells","authors":"Dieynaba Ndiaye,&nbsp;Marie Perceau,&nbsp;Mylène Lorcin,&nbsp;Flavien Denis,&nbsp;Laurent Gaté","doi":"10.1016/j.tiv.2024.105854","DOIUrl":"10.1016/j.tiv.2024.105854","url":null,"abstract":"<div><p>Among antifungal agents used in pharmaceuticals and personal care products, the synthetic azole climbazole (CBZ; 1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutan-2-one) acts on the fungus <em>Malassezia</em>. Despite concerns surrounding its effects on health, based on alterations to reproduction and steroidogenesis found in fish, little is known about its mechanism of action as an endocrine disrupting chemical (EDC) in mammalian cells.</p><p>In this study, using OECD test guidelines, we investigated the effects of CBZ (i) in H295R cells, on the production of estradiol and testosterone, as well as intermediate metabolites in steroidogenesis pathway, and (ii) in HeLa9903 and AR-EcoScreen cell lines, on the transactivation of estrogen and androgen receptors.</p><p>Our results are the first evidence in H295R cells, that CBZ treatment (from 0.3 μM) decreased secreted levels of testosterone and estradiol. This was associated with reduced 17α-hydroxypregnenolone and 17α-hydroxyprogesterone levels. The altered levels of these metabolites were associated with a decrease in cytochrome P450 17α-hydroxylase/17,20-lyase (Cyp17A1) activity without any effect on its protein level. CBZ was also found to exert antagonistic effects toward androgen and estrogen α receptors. These results give insights into the toxicological mechanism of action of CBZ. Many azoles share structural similarities; therefore, caution should be adopted due to their potential toxicity.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105854"},"PeriodicalIF":3.2,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141132502","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":"Nirmatrelvir has detrimental effects on sperm function by altering the PI3K/PDK1/AKT signaling pathway","authors":"Eun-Ju Jung ,&nbsp;Jae-Hwan Jo ,&nbsp;Claudine Uwamahoro ,&nbsp;Seung-Ik Jang ,&nbsp;Ju-Mi Hwang ,&nbsp;Woo-Jin Lee ,&nbsp;Jeong-Won Bae ,&nbsp;Do-Yeal Ryu ,&nbsp;Woo-Sung Kwon","doi":"10.1016/j.tiv.2024.105848","DOIUrl":"10.1016/j.tiv.2024.105848","url":null,"abstract":"<div><p>Nirmatrelvir (NMV) is a recently developed selective inhibitor of the main protease of Sars-Cov-2 that reduces the severity of infection. Despite its widespread use and various side effects, NMV's effect on male fertility is still unclear. This study was thus established to investigate how NMV affects male fertility. For experiments, Duroc spermatozoa were incubated with various concentrations of NMV (0, 0.1, 1, 10, 50, and 100 μM). Then, sperm motility, motion kinematics, capacitation status, intracellular ATP level, and cell viability were evaluated. In addition, the expression levels of phospho-PKA substrates, tyrosine-phosphorylated proteins, and PI3K/PDK1/AKT signaling pathway-related proteins were measured by western blotting. Our results showed that sperm motility, motion kinematics, proportion of capacitated spermatozoa, and intracellular ATP level were significantly decreased by NMV in a dose-dependent manner. Moreover, PKA activation was significantly suppressed by NMV, and expression levels of PI3K, phospho-PDK1, AKT, and phospho-AKT (Thr³⁰⁸ and Ser⁴⁷³) were significantly increased in a dose-dependent manner. Combining these findings, it is suggested that NMV has detrimental effects on sperm function by inducing abnormal changes in the PI3K/PDK1/AKT signaling pathway, resulting in PKA deactivation. Therefore, there is a need to pay particular attention to its male reproductive toxicity when NMV is administered.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105848"},"PeriodicalIF":3.2,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077327","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":"Unveiling the intricacies of BPA and BPS: comprehensive insights into its toxic effects using a cutting-edge microphysiological system","authors":"Melissa Dibbernn Ganzerla ,&nbsp;Nathalia de Carvalho Indolfo ,&nbsp;Larissa Cleres Moreira Oliveira ,&nbsp;Tabata Renee Doratioto ,&nbsp;Thayná Mendonça Avelino ,&nbsp;Rafael Junior de Azevedo ,&nbsp;Larissa Bueno Tofani ,&nbsp;Maiara Ferreira Terra ,&nbsp;Giovanna Blazutti Elias ,&nbsp;Irene Layane de Sousa ,&nbsp;Marcos Rodrigo Alborguetti ,&nbsp;Silvana Aparecida Rocco ,&nbsp;Kelen Fabiola Arroteia ,&nbsp;Ana Carolina Migliorini Figueira","doi":"10.1016/j.tiv.2024.105849","DOIUrl":"10.1016/j.tiv.2024.105849","url":null,"abstract":"<div><p>Concerns over Bisphenol A (BPA) and its substitute, Bisphenol S (BPS), have led to innovative exploration due to potential adverse health effects. BPS, replacing BPA in some regions to avoid toxic impacts, remains insufficiently studied. Besides this, the organ-on-a-chip technology emerges as a transformative solution in drug discovery and chemiclas toxicity testing, minimizing costs and aligning with ethical standards by reducing reliance on animal models, by integrating diverse tissues and dynamic cell environments enhances precision in predicting organ function.</p><p>Here, we employ a 3-organ-on-a-chip microfluidic device with skin, intestine, and liver cultures to assess the effects of BPA and BPS via topical and oral administration. Our evaluation focused on gene markers associated with carcinogenicity, systemic toxicity, and endocrine disruption. BPA exhibited expected absorption profiles, causing liver injury and genetic modulation in related pathways. BPS, a safer alternative, induced adverse effects on gene expression, particularly in topical absorption, with distinct absorption patterns. Our findings underscore the urgency of addressing BPA and BPS toxicity concerns, highlighting the crucial role of organ-on-a-chip technology in understanding associated health risks. The study promotes the organ-on-a-chip methodology as a valuable tool for safe drug development and disease treatments, offering a novel liver toxicity screening alternative to traditional animal tests. This contributes to advancing comprehension of the biological effects of these compounds, fostering improved safety assessments in human health.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"98 ","pages":"Article 105849"},"PeriodicalIF":3.2,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077329","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}