Toxicology in Vitro最新文献_第4页

Chlorpyrifos-oxon induced neuronal cell death via endoplasmic reticulum stress-triggered apoptosis pathways 毒死蜱通过内质网应激触发的细胞凋亡途径诱导神经细胞死亡

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-07 DOI: 10.1016/j.tiv.2024.105939

Baihuan Feng , Jingchun Lu , Wei Jiang , Nani Xu , Wenjun Sun

{"title":"Chlorpyrifos-oxon induced neuronal cell death via endoplasmic reticulum stress-triggered apoptosis pathways","authors":"Baihuan Feng , Jingchun Lu , Wei Jiang , Nani Xu , Wenjun Sun","doi":"10.1016/j.tiv.2024.105939","DOIUrl":"10.1016/j.tiv.2024.105939","url":null,"abstract":"<div><p>Chlorpyrifos (CPF) is one of the organophosphorus pesticides widely used throughout the world. Epidemiological studies suggested a link between CPF exposure and neurologic disorders, while the molecular mechanisms remain inconclusive. In the present study, we investigated the impacts of chlorpyrifos-oxon (CPO), the major toxic CPF metabolite, on cell apoptosis, and explored possible mechanism associated with endoplasmic reticulum (ER) stress in SH-SY5Y cells. Results showed that CPO exposure induced dose-dependent apoptosis and expression of ER stress-related proteins in SH-SY5Y cells. Pretreatment with 4-PBA (an ER stress inhibitor) effectively inhibited the expression of GRP78, GRP94, p-IRE1α, and XBP1-s, and apoptotic events. Pretreatment with STF-083010 (an IRE1α inhibitor) partially attenuated CPO-induced apoptosis. In addition, CPO exposure significantly evoked the generation of reactive oxygen species (ROS) which could be eliminated by pretreatment of 4-PBA. Of note, buffering the ROS generation with antioxidant NAC had little impact on the expression of p-IRE1α, and only partially attenuated CPO-induced apoptosis. In contrast, co-pretreatment with NAC and STF-083010 effectively inhibited CPO-induced apoptotic events. Collectively, our results indicate that CPO exposure exerts neuronal cytotoxicity via ER stress downstream-regulated IRE1α/XBP1 signaling pathway and ROS generation-triggered apoptosis. These findings highlight the role of ER stress in CPF-induced neurotoxicity, and provide a promising target for the intervention of organophosphate-associated neurodegenerative diseases.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105939"},"PeriodicalIF":2.6,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167214","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

Applying cell painting in non-tumorigenic breast cells to understand impacts of common chemical exposures 应用非致癌乳腺细胞中的细胞绘画来了解常见化学品暴露的影响。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-06 DOI: 10.1016/j.tiv.2024.105935

Anagha Tapaswi , Nicholas Cemalovic , Katelyn M. Polemi , Jonathan Z. Sexton , Justin A. Colacino

{"title":"Applying cell painting in non-tumorigenic breast cells to understand impacts of common chemical exposures","authors":"Anagha Tapaswi , Nicholas Cemalovic , Katelyn M. Polemi , Jonathan Z. Sexton , Justin A. Colacino","doi":"10.1016/j.tiv.2024.105935","DOIUrl":"10.1016/j.tiv.2024.105935","url":null,"abstract":"<div><p>The general population is exposed to many chemicals which have putative, but incompletely understood, links to breast cancer. Cell Painting is a high-content imaging-based in vitro assay that allows for unbiased measurements of concentration-dependent effects of chemical exposures on cellular morphology. We used Cell Painting to measure effects of 16 human exposure relevant chemicals, along with 21 small molecules with known mechanisms of action, in non-tumorigenic mammary epithelial cells, the MCF10A cell line. Using CellProfiler image analysis software, we quantified 3042 morphological features across approximately 1.2 million cells. We used benchmark concentration modeling to identify features both conserved and different across chemicals. Benchmark concentrations were compared to exposure biomarker concentration measurements from the National Health and Nutrition Examination Survey to assess which chemicals induce morphological alterations at human-relevant concentrations. We found significant feature overlaps between chemicals, including similarities between the organochlorine pesticide DDT metabolite p,p’-DDE and an activator of Wnt signaling CHIR99201. We validated these findings by assaying the activation of Wnt, as reflected by translocation of ꞵ-catenin, following p’-p’ DDE exposure. Consistent with Wnt signaling activation, low concentration p’,p’-DDE (25 nM) significantly enhanced the nuclear translocation of ꞵ-catenin. Overall, these findings highlight the ability of Cell Painting to enhance mode-of-action studies for toxicants which are common in our environment but incompletely characterized with respect to breast cancer risk.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105935"},"PeriodicalIF":2.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146882","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

Effects of polystyrene micro- and nanoplastics on androgen- and estrogen receptor activity and steroidogenesis in vitro 聚苯乙烯微塑料和纳米塑料对雄激素和雌激素受体活性以及体外类固醇生成的影响。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-05 DOI: 10.1016/j.tiv.2024.105938

Jeske van Boxel , Rani R.J. Khargi , Sandra M. Nijmeijer , Manuel T. Heinzelmann , Daniel Da Costa Pereira , Marja H. Lamoree , Majorie B.M. van Duursen

{"title":"Effects of polystyrene micro- and nanoplastics on androgen- and estrogen receptor activity and steroidogenesis in vitro","authors":"Jeske van Boxel , Rani R.J. Khargi , Sandra M. Nijmeijer , Manuel T. Heinzelmann , Daniel Da Costa Pereira , Marja H. Lamoree , Majorie B.M. van Duursen","doi":"10.1016/j.tiv.2024.105938","DOIUrl":"10.1016/j.tiv.2024.105938","url":null,"abstract":"<div><p>While many plastic additives show endocrine disrupting properties, this has not been studied for micro- and nanoplastics (MNPs) particles despite their ubiquitous presence in humans. The objective of this study was to determine the effects of various sizes and concentrations of polystyrene (PS)-MNPs (50–10,000 nm, 0.01–100 μg/mL) on estrogen- and androgen receptor (ER and AR) activity and steroidogenesis <em>in vitro</em>. Fluorescent (F)PS-MNPs of ≤1000 nm were internalized in VM7 and H295R cells and FPS-MNPs ≤200 nm in AR-ecoscreen cells. H295R cells displayed the highest uptake and particles were closer to the nucleus than other cell types. None of the sizes and concentrations PS-MNPs tested affected ER or AR activity. In H295R cells, PS-MNPs caused some statistically significant changes in hormone levels, though these showed no apparent concentration or size-dependent patterns. Additionally, PS-MNPs caused a decrease in estriol (E3) with a maximum of 37.5 % (100 μg/mL, 50 nm) and an increase in gene expression of oxidative stress markers GPX1 (1.26-fold) and SOD1 (1.23-fold). Taken together, our data show limited endocrine-disrupting properties of PS-MNPs <em>in vitro</em>. Nevertheless the importance of E3 in the placenta warrants further studies in the potential effects of MNPs during pregnancy.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105938"},"PeriodicalIF":2.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887233324001681/pdfft?md5=4ec13720471a591225d5aefbd853a820&pid=1-s2.0-S0887233324001681-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alteration in folate carrier expression via histone deacetylase inhibition in BeWo human placental choriocarcinoma cells 通过抑制组蛋白去乙酰化酶改变 BeWo 人胎盘绒毛膜癌细胞中叶酸载体的表达。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-03 DOI: 10.1016/j.tiv.2024.105934

Yuki Miyazawa , Ayako Furugen , Ryoichi Aoyagi , Haruna Kosugi , Ayako Nishimura , Takeshi Umazume , Katsuya Narumi , Masaki Kobayashi

{"title":"Alteration in folate carrier expression via histone deacetylase inhibition in BeWo human placental choriocarcinoma cells","authors":"Yuki Miyazawa , Ayako Furugen , Ryoichi Aoyagi , Haruna Kosugi , Ayako Nishimura , Takeshi Umazume , Katsuya Narumi , Masaki Kobayashi","doi":"10.1016/j.tiv.2024.105934","DOIUrl":"10.1016/j.tiv.2024.105934","url":null,"abstract":"<div><p>Folates are essential nutrients for fetal development during pregnancy. Valproic acid (VPA), an inhibitor of histone deacetylases (HDACs), alters the expression of folate carriers in placental cells; however, the underlying mechanisms remain unclear. Here, we aimed to determine the profiles of folate carriers (folate receptor alpha [<em>FOLR1</em>], solute carrier [<em>SLC</em>]-<em>19A1</em>, and <em>SLC46A1</em>) after inhibition of HDACs, especially class I and IIa HDACs, using different inhibitors and gene knockdown tests. Quantitative polymerase chain reaction revealed that BeWo cells (a trophoblast model) expressed HDACs and folate carriers, similar to human placental villi. <em>FOLR1</em> expression was upregulated by VPA, apicidin, and trichostatin A, but downregulated by MS-275 after 24 h treatment. VPA and apicidin upregulated the expression of <em>SLC46A1</em>. These inhibitors downregulated <em>SLC19A1</em> expression. TMP269 (a class IIa inhibitor) did not affect folate carrier levels. <em>HDAC1/2</em> knockdown upregulated <em>FOLR1</em> and <em>SLC46A1</em> levels, whereas <em>HDAC1/3</em> knockdown downregulated <em>FOLR1</em> levels. Our findings suggest that the pharmacological inhibition of class I HDACs alters the expression of folate carriers in BeWo cells. By contrast, HDAC inhibitors exert different regulatory effects on folate carriers. Moreover, HDAC1/2 inhibition may be a potential mechanism involved in altering <em>FOLR1</em> and <em>SLC46A1</em> levels.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105934"},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141676","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

Risperidone-induced bioenergetic disruption in the isolated human peripheral blood monocytes 利培酮诱导的离体人类外周血单核细胞生物能紊乱。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-03 DOI: 10.1016/j.tiv.2024.105936

Bandar Alenazi , Huda A. Al Doghaither , Ayat B. Al-Ghafari , Ekramy M. Elmorsy

{"title":"Risperidone-induced bioenergetic disruption in the isolated human peripheral blood monocytes","authors":"Bandar Alenazi , Huda A. Al Doghaither , Ayat B. Al-Ghafari , Ekramy M. Elmorsy","doi":"10.1016/j.tiv.2024.105936","DOIUrl":"10.1016/j.tiv.2024.105936","url":null,"abstract":"<div><p>Risperidone (RIS) is a widely used antipsychotic drug with reported alteration in immune response. The current study investigated mitochondrial disruption as the underlying mechanism of RIS-induced immunotoxicity in isolated human peripheral blood monocytes (hPBM). RIS was cytotoxic to hPBM in exposure duration and concentration-dependent patterns. Functionally, RIS was shown to increase the release of IL-6, TNF-α, and IL-8 with a decrease in test particle phagocytosis in concertation and exposure time-based patterns. It was found that RIS decreased ATP production in isolated monocytes' mitochondria, with an estimated EC50 of around 70 μM after 24 h with parallel inhibition of mitochondrial complexes I and III activities and decreased mitochondrial membrane potential and oxygen consumption rates with increased lactate production from by the treated cells in comparison to controls. Structurally, RIS in 100 μM concentration significantly increased the mitochondrial membrane fluidity with significant increase in increased unsaturated/saturated fatty acids ratios of the mitochondrial membranes of the treated cells. Interestingly, water-soluble CoQ10 formulation significantly decreased the cytotoxic effect of RIS and improved the phagocytic activity of RIS-treated cells. To conclude, the current data suggests mitochondrial disruption as the underlying mechanism of RIS-induced immunotoxicity with shown protective effect of water-soluble CoQ10 formulation.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105936"},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141678","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

Can TK-TD modelling bridge the gap between in vitro and in vivo mammalian toxicity data? TK-TD 模型能否弥合体外和体内哺乳动物毒性数据之间的差距？

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-03 DOI: 10.1016/j.tiv.2024.105937

Thomas Martin , Mark E. Hodson , Helen Thompson , Victoria Hutter , Roman Ashauer

{"title":"Can TK-TD modelling bridge the gap between in vitro and in vivo mammalian toxicity data?","authors":"Thomas Martin , Mark E. Hodson , Helen Thompson , Victoria Hutter , Roman Ashauer","doi":"10.1016/j.tiv.2024.105937","DOIUrl":"10.1016/j.tiv.2024.105937","url":null,"abstract":"<div><p>Repeated dietary dose testing is used to assess longer term toxicity of chemicals, such as pesticides, to mammals. However, the internal pesticide concentration varies significantly as feeding rate relative to body size fluctuates over time. Toxicokinetic-toxicodynamic (TK-TD) models can estimate internal toxicant concentration over time and link this directly to observed effects on endpoints such as the growth rate of laboratory rats. Using TK-TD models it is therefore possible to predict the effects that would result from a constant internal concentration of a pesticide. This presents the possibility of comparison with data from <em>in vitro</em> experiments, potentially facilitating quantitative <em>in vitro</em> to <em>in vivo</em> extrapolation (QIVIVE). We used <em>in vivo</em> TK-TD models to identify relevant internal concentrations and then estimated the experimental conditions required to replicate these in cultured cells, using <em>in vitro</em> TK models. Cell population growth was measured, with a view to extrapolating through time and comparing effect sizes with <em>in vivo</em> predictions. However, observed cell proliferation was not significantly affected by the tested concentrations of any of the five pesticides in this study and so extrapolation was not possible. In light of this negative result, we highlight areas for future work towards QIVIVE of graded sublethal effects in mammals. The most pressing objective is improving the accuracy of <em>in vivo</em> TK predictions, which could be achieved with dietary dosing in TK studies.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105937"},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141677","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

Corrigendum to “Novel Diphenyl urea derivative serves as an inhibitor on human lung cancer cell migration by disrupting EMT via Wnt/β-catenin and PI3K/Akt signaling” [Toxicology in Vitro 69 (2020) 105000] 新型二苯基脲衍生物通过 Wnt/β-catenin 和 PI3K/Akt 信号转导破坏 EMT，从而成为人类肺癌细胞迁移的抑制剂》[《体外毒理学》69 (2020) 105000]的更正。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-02 DOI: 10.1016/j.tiv.2024.105923

Bingling Dai , Mengying Fan , Runze Yu , Qi Su , Bo Wang , Tianfeng Yang , Feng Liu , Yanmin Zhang

引用次数: 0

Effect of cannabidiol and hemp extract on viability and function of hepatocytes derived from human induced pluripotent stem cells 大麻二酚和大麻提取物对人类诱导多能干细胞肝细胞活力和功能的影响。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-02 DOI: 10.1016/j.tiv.2024.105933

Kayla Campasino, Miranda R. Yourick, Yang Zhao, Estatira Sepehr, Cory Vaught, Jeffrey J. Yourick, Robert L. Sprando, Xiugong Gao

{"title":"Effect of cannabidiol and hemp extract on viability and function of hepatocytes derived from human induced pluripotent stem cells","authors":"Kayla Campasino, Miranda R. Yourick, Yang Zhao, Estatira Sepehr, Cory Vaught, Jeffrey J. Yourick, Robert L. Sprando, Xiugong Gao","doi":"10.1016/j.tiv.2024.105933","DOIUrl":"10.1016/j.tiv.2024.105933","url":null,"abstract":"<div><p>Since the passage of the 2018 Agriculture Improvement Act (2018 Farm Bill), the number of products containing cannabis-derived compounds available to consumers have rapidly increased. Potential effects on liver function as a result from consumption of products containing cannabidiol (CBD), including hemp extracts, have been observed but the mechanisms for the effects are not fully understood. In this study, hepatocytes derived from human induced pluripotent stem cells (iPSCs) were used to evaluate potential hepatic effects of CBD and hemp extract at exposure concentrations ranging from 0.1 to 30 μM. Despite that a significant reduction in cell viability occurred only in the 30 μM group for both CBD and hemp extract, significant changes to cytochrome P450 activity, mitochondrial membrane potential, and lipid accumulation occurred within the concentration range of 0.1–3 μM for both CBD and hemp extract. Albumin and urea production, caspase 3/7 activity, and intracellular glutathione were significantly affected within the concentration range of 3–30 μM by CBD or hemp extract. These findings indicate that CBD and hemp extract can alter hepatic function and metabolism. The current study contributes data to help inform the evaluation of potential hepatotoxic effects of products containing cannabis-derived compounds.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105933"},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887233324001632/pdfft?md5=f55906ed981f1843eafa92c57a0cd670&pid=1-s2.0-S0887233324001632-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reliability and relevance of the ES®-RHE model for in vitro skin irritation test application 用于体外皮肤刺激性测试的 ES®-RHE 模型的可靠性和相关性。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-01 DOI: 10.1016/j.tiv.2024.105932

C.A. Mini, G. Ballestero, C.C. Munari, D.B. Carrão, B.C. Fonseca, N.C. Albuquerque, F. Marquele-Oliveira

{"title":"Reliability and relevance of the ES®-RHE model for in vitro skin irritation test application","authors":"C.A. Mini, G. Ballestero, C.C. Munari, D.B. Carrão, B.C. Fonseca, N.C. Albuquerque, F. Marquele-Oliveira","doi":"10.1016/j.tiv.2024.105932","DOIUrl":"10.1016/j.tiv.2024.105932","url":null,"abstract":"<div><h3>Introduction</h3><p><em>In vitro</em> methods have been widely used to assess adverse effects. Reconstructed Human Epidermis (RHE) poses as a fascinating test system employed to assess the dermal irritation hazard potential of chemicals. Although several RHE models are reported in the OECD Test Guideline No. 439, the OECD Document No. 220 encourages the scientific community to develop and validate new RHE test systems due to its relevance for socio-economic advancement.</p></div><div><h3>Methods</h3><p>Following the criteria documented in the OECD No. 220, a blind study for skin irritation (OECD 439) was conducted employing the Minimum List of Reference Chemicals for Determination of Reproducibility and Predictive Capacity using ES®-RHE. Structural and functional characteristics were assessed alongside the prediction model.</p></div><div><h3>Results</h3><p>The model has shown reproducibility of optical density and barrier function, similarly to internationally validated methods. Furthermore, it shows the cell layers' development and differentiation ability due to Cytokeratin14, Cytokeratin10, and filaggrin expression. The prediction model resulted in sensitivity, specificity and accuracy rates of 100, 70, and 77 %, respectively.</p></div><div><h3>Conclusions</h3><p>The ES®-RHE demonstrated reliability and relevance, with similar structural and functional characteristics comparable to internationally validated models, in addition to the accepted predictive capacity according to OECD required minimum criteria, thus confirming the suitability of the national ES®-RHE in the hazard prediction of dermal irritation based on OECD Test Guideline No. 439.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105932"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127362","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

Assessment of ursolic acid effect on in vitro model of cardiac fibrosis 评估熊果酸对体外心脏纤维化模型的影响

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-08-30 DOI: 10.1016/j.tiv.2024.105924

Samane Sadat Hosseiny , Zahra Esmaeili , Zeinab Neshati

{"title":"Assessment of ursolic acid effect on in vitro model of cardiac fibrosis","authors":"Samane Sadat Hosseiny , Zahra Esmaeili , Zeinab Neshati","doi":"10.1016/j.tiv.2024.105924","DOIUrl":"10.1016/j.tiv.2024.105924","url":null,"abstract":"<div><p>This study aimed to evaluate the effects of ursolic acid (UA) on Angiotensin II (Ang II)-treated neonatal rat cardiac fibroblasts (rCFs) as an <em>in vitro</em> model of cardiac fibrosis. The rCFs were isolated from two-day-old neonatal rats. An <em>in vitro</em> model of cardiac fibrosis was established using 500 nm Ang II treatment for 48 h. The cells were then treated with 5 and 10 μM of UA for 24 and 48 h. Masson's trichrome staining, hydroxyproline content assay, scratch assay, apoptosis assay, measurements of superoxide dismutase (SOD) and malondialdehyde (MDA) levels, real-time PCR, immunocytology and western blotting, were employed to assess the impact of UA. Ang II induced fibrosis in rCFs, as evidenced by the examination of various fibrotic markers. Upon treatment with 5 and 10 μM of UA, the amount of fibrosis in Ang II-treated rCFs was significantly decreased, so that the hydroxyproline concentration was reduced to 0.3 and 0.7 times, respectively. The RNA expression of the <em>Col1a1, Col3a1, Tgfb1, Acta2</em> and <em>Mmp2</em> genes had a decrease as well as <em>Nrf2</em> and <em>HO-1</em> had an increase after UA treatment. UA could lessen the harmful effects of cardiac fibrosis in a dose- and time-dependent manner, due to its antiapoptotic, antioxidant and cardioprotective properties. This suggests the potential of UA for treatment of cardiac fibrosis.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105924"},"PeriodicalIF":2.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114737","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