Toxicology in Vitro最新文献_第8页

Oxidative Stress, Lysosomal Permeability, and Mitochondrial-Derived Vesicles Induced in NL-20 Human Bronchial Cells Exposed to Benzo[ghi]Perylene 暴露于苯并[ghi]苝的NL-20人支气管细胞诱导的氧化应激、溶酶体通透性和线粒体来源的囊泡。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-12-17 DOI: 10.1016/j.tiv.2024.105999

López-Pérez Lizardo , Roldán-Barreto Elisa , Xochiteotzin-Reyes Tania , Torres-Flores Ulises , Licea-Quintero Brandon , Monroy-Quintana Regina , Corona Juan Carlos , Zaragoza-Ojeda Montserrat , Arenas-Huertero Francisco

{"title":"Oxidative Stress, Lysosomal Permeability, and Mitochondrial-Derived Vesicles Induced in NL-20 Human Bronchial Cells Exposed to Benzo[ghi]Perylene","authors":"López-Pérez Lizardo , Roldán-Barreto Elisa , Xochiteotzin-Reyes Tania , Torres-Flores Ulises , Licea-Quintero Brandon , Monroy-Quintana Regina , Corona Juan Carlos , Zaragoza-Ojeda Montserrat , Arenas-Huertero Francisco","doi":"10.1016/j.tiv.2024.105999","DOIUrl":"10.1016/j.tiv.2024.105999","url":null,"abstract":"<div><div>Benzo[<em>ghi</em>] perylene (b[<em>ghi</em>]p) is classified as non-carcinogenic to humans, and there are currently no occupational exposure models available to identify its effects. The aim of this work was to evaluate the effect of b[<em>ghi</em>]p on the lysosomes of NL-20 cells (a human bronchial cell line) exposed to 4.5 μM for 3 h. The effect was evaluated through an ultrastructural evaluation, morphological changes, and acridine orange staining of lysosomes. Superoxide was quantified; and SOD1, cathepsin B, LAMP1, galectin-3 and LC3α/β, and Rab7 expression was evaluated by immunocytochemistry. The expression of genes related to oxidative stress responses (NRF2, NQO1, HMOX1 and PRDX1) and genes related to autophagy (ULK1, ATG9, BCN1, VMP1, TMEM41B and p62) were quantified by RT-qPCR. The ultrastructural evaluation revealed an increase in autophagic vesicles and phagophores in cells exposed to b[<em>ghi</em>]p, as well as vesicles derived from mitochondria. Based on morphology, there were vesicles in the cytoplasm. B[<em>ghi</em>]p significantly decreased the number of lysosomes (<em>p</em> < 0.05), and NAC reverse this effect (p < 0.05). Superoxide production was observed from 30 min to 3 h (p < 0.05). Immunocytochemistry revealed increased galectin-3 and LC3α/β. All oxidative stress–related genes showed high expression (p < 0.05), and the expression of ATG9 gene was decreased (p < 0.05). These results demonstrate that b[<em>ghi</em>]p induces oxidative stress, responsible for producing the toxic effects in the lysosomes of NL-20 cells.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 105999"},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866438","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

Development of a human FaFg prediction system for polyphenols using human induced pluripotent stem cell-derived small intestinal epithelial cells 利用人体诱导多能干细胞衍生的小肠上皮细胞开发人体多酚 FaFg 预测系统。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-12-12 DOI: 10.1016/j.tiv.2024.105998

Shunta Shigemura, Takuya Kikuchi, Yuichi Ito, Osamu Morita, Kazutoshi Saito

{"title":"Development of a human FaFg prediction system for polyphenols using human induced pluripotent stem cell-derived small intestinal epithelial cells","authors":"Shunta Shigemura, Takuya Kikuchi, Yuichi Ito, Osamu Morita, Kazutoshi Saito","doi":"10.1016/j.tiv.2024.105998","DOIUrl":"10.1016/j.tiv.2024.105998","url":null,"abstract":"<div><div>Precise prediction of the fraction of compounds reaching the portal vein (<em>FaFg</em>) in humans, which could indicate the rate-limiting step of polyphenol metabolism, is particularly important for accurately evaluating the efficacy and safety of polyphenols. In this study, we aimed to develop a novel <em>in vitro</em> method to predict human <em>FaFg</em> of polyphenols using commercially available human induced pluripotent stem cell-derived small intestinal epithelial cells (hiPSC-SIECs). First, the chemicals were used at fixed test concentrations, considering their physicochemical properties and cytotoxicity. The apparent permeability coefficient (P<sub>app</sub>) values of the six tested polyphenols in hiPSC-SIECs were considerably higher than those of the seven tested pharmaceuticals, resulting in a poor correlation between P<sub>app</sub> in hiPSC-SIECs and human <em>FaFg</em>. A detailed assessment of the relationship between <em>in vitro</em> test concentration and metabolic activity suggested that the higher P<sub>app</sub> value of polyphenols would be due to inadequate reflection of phase II metabolism in the human intestine. By optimizing test concentrations to reflect enzymatic metabolism in the human intestine, a good correlation was observed between the P<sub>app</sub> values in hiPSC-SIECs and human <em>FaFg</em> for tested polyphenols and pharmaceuticals (R<sup>2</sup> = 0.81). The developed method could be useful for precisely predicting human <em>FaFg</em> of polyphenols.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 105998"},"PeriodicalIF":2.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824826","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

Airway organoids: 3D toxicology evaluation models in vitro of heated tobacco products for health risk 气道有机体：加热烟草制品健康风险体外三维毒理学评估模型。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-12-10 DOI: 10.1016/j.tiv.2024.105995

Xianglong Wang , Yushan Tian , Huan Chen , Hongwei Hou , Qingyuan Hu

{"title":"Airway organoids: 3D toxicology evaluation models in vitro of heated tobacco products for health risk","authors":"Xianglong Wang , Yushan Tian , Huan Chen , Hongwei Hou , Qingyuan Hu","doi":"10.1016/j.tiv.2024.105995","DOIUrl":"10.1016/j.tiv.2024.105995","url":null,"abstract":"<div><div>Cigarette smoking poses significant health risks, particularly to the airway, which consists predominantly of basal, club, and ciliated cells that are highly susceptible to damage from exogenous stimuli. Traditional <em>in vitro</em> toxicology relies on 2D cell cultures, which lack the structural complexity and functional relevance of airway architecture. As a novel category of tobacco products, the health implications of heated tobacco products (HTPs) remain largely unknown. To address this, 3D airway organoids were developed as a more physiologically relevant <em>in vitro</em> model for evaluating the toxicity of HTPs. Airway organoids derived from mouse lungs were induced to differentiate into various airway cell types and exposed to HTP aerosols. The exposure impaired organoid growth, reduced cell viability, and altered the proportions of secretory, basal, and ciliated cells, effectively replicating the complex cellular damage observed <em>in vivo</em>. Additionally, typical adverse outcomes, such as oxidative stress, inflammation, and genetic toxicity, were induced, paralleling findings from conventional 2D models. These results established the airway organoids as a viable alternative to animal testing for toxicological studies and offer critical insights into the respiratory health risks associated with HTPs.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 105995"},"PeriodicalIF":2.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819894","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

Essential oil from Ocimum carnosum induces ROS mediated mitochondrial dysfunction and intrinsic apoptosis in HL-60 cells 鹿茸精油诱导ROS介导的HL-60细胞线粒体功能障碍和内在凋亡。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-12-07 DOI: 10.1016/j.tiv.2024.105988

Madhunika Agrawal , A.K. Saxena , Satyam Kumar Agrawal

{"title":"Essential oil from Ocimum carnosum induces ROS mediated mitochondrial dysfunction and intrinsic apoptosis in HL-60 cells","authors":"Madhunika Agrawal , A.K. Saxena , Satyam Kumar Agrawal","doi":"10.1016/j.tiv.2024.105988","DOIUrl":"10.1016/j.tiv.2024.105988","url":null,"abstract":"<div><div>The present study demonstrates that essential oil from <em>Ocimum carnosum</em> (EOC), possesses potent cytotoxic properties against human promyelocytic leukemia HL-60 cells. The results demonstrated a concentration- and time-dependent reduction in cell viability, with an IC<sub>50</sub> value of 0.029 μl/ml after 24 h. Further mechanistic studies revealed that EOC induces apoptosis, a regulated form of cell death in HL-60 cells. This was evidenced by morphological changes characteristic of apoptosis, including cell shrinkage, membrane blebbing, and nuclear condensation. Additionally, flow cytometric analysis demonstrated a significant increase in the sub-G<sub>0</sub> cell population, indicative of DNA fragmentation. The mitochondrial pathway of apoptosis appears to be involved in EOC-induced cell death. A loss of mitochondrial membrane potential and the subsequent release of cytochrome <em>c</em> into the cytosol were observed. Pronounced quantity of cytosolic cytochrome <em>c</em> was associated with Bcl-2 depletion. Moreover, cytochrome <em>c</em>, in conjunction with other apoptotic factors, activates caspases, a family of cysteine proteases that execute cell death. These findings collectively indicate that EOC possesses promising anti-cancer properties through the induction of apoptosis via a mitochondrial-dependent pathway. However, further studies are required to elucidate the precise molecular mechanisms underlying EOC's cytotoxic effects and to evaluate its therapeutic potential <em>in vivo</em>.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 105988"},"PeriodicalIF":2.6,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803493","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

Porcupine inhibitors LGK-974 and ETC-159 inhibit Wnt/β-catenin signaling and result in inhibition of the fibrosis 豪猪抑制剂LGK-974和ETC-159抑制Wnt/β-catenin信号传导，导致纤维化抑制。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-12-06 DOI: 10.1016/j.tiv.2024.105986

Ayşe Koçak , Semih Gülle , Merih Birlik

{"title":"Porcupine inhibitors LGK-974 and ETC-159 inhibit Wnt/β-catenin signaling and result in inhibition of the fibrosis","authors":"Ayşe Koçak , Semih Gülle , Merih Birlik","doi":"10.1016/j.tiv.2024.105986","DOIUrl":"10.1016/j.tiv.2024.105986","url":null,"abstract":"<div><h3>Objectives</h3><div>We evaluated potential therapeutic efficacy of LGK-974 and ETC-159 in fibrotic scleroderma cells.</div></div><div><h3>Methods</h3><div>Primary scleroderma dermal fibroblast cells of mouse origin (SSc fibroblasts) and primary fibrotic lung fibroblast cells of human origin (CCL-191) were used in this study. PORCN inhibitors LGK-974 (S7143, 1 μM; Selleckchem, USA) and ETC-159 (S7143, 10 μM; Selleckchem, USA) were used. The possible therapeutic effects of LGK-974 and ETC-159 on scleroderma cells and fibrosis cells were examined. Cell viability experiments were performed for each substance, and the expression levels of WNT and fibrosis marker genes were determined by qPCR. Western blotting was also used to determine collagen, fibronectin and α-SMA protein markers.</div></div><div><h3>Results</h3><div>This study showed that LGK-974 and ETC-159 probable protein-cysteine N-palmitoyltransferase porcupine (PORCN) inhibitors exert potent antifibrotic effects and reduce fibrosis by modulating the TGF-β signaling pathway in scleroderma cells. Using LGK-974 and ETC-159 PORCN inhibitors, either alone or in combination, can affect collagen deposition and fibrosis in patients with SSc.</div></div><div><h3>Conclusions</h3><div>LGK-974 and ETC-159 may be a possible long-term therapeutic target for scleroderma.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 105986"},"PeriodicalIF":2.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796423","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 2,4-dichlorophenoxyacetic acid (2,4-D), isolated and in a formulated product, on the functional parameters of isolated rat liver mitochondria 2,4-二氯苯氧乙酸（2,4- d）对离体大鼠肝脏线粒体功能参数的影响

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-12-04 DOI: 10.1016/j.tiv.2024.105984

L.R.F. Polido , C.A. Miranda , D.A. França , F.E. Mingatto , L.C. Pereira

{"title":"Effects of 2,4-dichlorophenoxyacetic acid (2,4-D), isolated and in a formulated product, on the functional parameters of isolated rat liver mitochondria","authors":"L.R.F. Polido , C.A. Miranda , D.A. França , F.E. Mingatto , L.C. Pereira","doi":"10.1016/j.tiv.2024.105984","DOIUrl":"10.1016/j.tiv.2024.105984","url":null,"abstract":"<div><div>2,4-Dichlorophenoxyacetic acid (2,4-D) is a widely used herbicide with known implications for environmental and biological systems. Previous studies indicate its potential to interact with cellular structures, potentially impacting cellular energy and metabolism. This study aimed to investigate the toxicological effects of this molecule on isolated rat liver mitochondria, evaluating both isolated and formulated 2,4-D to comprehend the differential impacts on mitochondrial function. Our investigations did not reveal significant induction of oxidative stress, mitochondrial swelling or impacts on mitochondrial respiration; however, exposure to both forms of 2,4-D affected mitochondrial membrane integrity and function in a concentration-dependent manner, notably impacting mitochondrial ATP levels and membrane potential. Comparatively, the formulated product showed toxicity at lower concentrations regarding interaction with membranes and ATP levels (from 0.4 μM on) and isolated 2,4-D showed toxicity at lower concentrations regarding membrane potential dissipation (from 10 μM on). Notably, the effects on ATP levels and membrane fluidity suggest interactions within the mitochondrial lipid bilayer. The findings highlight that excipients in the commercial formulation of 2,4-D potentially alter its effects, underlining the importance of evaluating not only active ingredients but also formulations.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 105984"},"PeriodicalIF":2.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792856","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

β-Arbutin and cisplatin: A combined approach to modulating apoptosis, cell viability, and migration in bladder cancer cells β-熊果苷和顺铂：调节膀胱癌细胞凋亡、细胞活力和迁移的联合方法。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-12-03 DOI: 10.1016/j.tiv.2024.105985

Emine Terzi , Beyza Ecem Oz-Bedir , Elif Ercan , Tuba Ozdemir-Sanci , Shahla Jafarova , Tuba Aydin

{"title":"β-Arbutin and cisplatin: A combined approach to modulating apoptosis, cell viability, and migration in bladder cancer cells","authors":"Emine Terzi , Beyza Ecem Oz-Bedir , Elif Ercan , Tuba Ozdemir-Sanci , Shahla Jafarova , Tuba Aydin","doi":"10.1016/j.tiv.2024.105985","DOIUrl":"10.1016/j.tiv.2024.105985","url":null,"abstract":"<div><div>One of the preferred treatments for bladder cancer, one of the most common cancers worldwide, is cisplatin-based chemotherapy. Since most tumor cells show cisplatin resistance, it is very important to discover new agents without adverse side effects. β-arbutin, a hydroquinone-β-D-glucopyranoside, has biological properties such as antioxidant, antimicrobial, anti-inflammatory, and anticancer, and is a phytochemical widely used as a skin whitener. In this study, β-arbutin was purified from the animal feed plant Onobrychis buhseana Boiss. (sainfoin). The study aimed to investigate the combined effects of cisplatin, a clinically used chemotherapeutic agent, and β-arbutin on HT-1376 bladder cancer cells for apoptosis, cell viability, and migration. In the study, after HT-1376 bladder cancer cells were cultured, optimum β-arbutin and cisplatin doses were determined on HT-1376 cells using the WST-1 test. To determine the apoptotic and migratory effects, flow cytometry and wound healing assays were performed. In HT-1376 cells, β-Arbutin led to greater apoptotoic and migratory effects when used alone and combined with Cisplatin (<em>p</em> < 0.0001 for apoptotic and migratory effects treated with β-Arbutin alone, p < 0.0001 for apoptotic and migratory effects when combined with Cisplatin). As a result, it can be suggested that β-arbutin may be a good drug candidate for treating bladder cancer.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 105985"},"PeriodicalIF":2.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787767","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

Mictlan-D3: A novel medium sized RGD-Disintegrin obtained from Crotalus mictlantecuhtli venom, in vitro tested against human breast Cancer and endothelial cells Mictlan-D3：从Crotalus mictlantecuhtli毒液中提取的一种新型中等大小的rpd -崩解素，体外测试了其对人乳腺癌和内皮细胞的作用。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-12-02 DOI: 10.1016/j.tiv.2024.105987

E. Rivas-Mercado , E. Neri-Castro , V. Zarzosa , L. Hernández-Orihuela , F. Olvera-Rodríguez , J.D. Torres-Garza , L. Garza-Ocañas

{"title":"Mictlan-D3: A novel medium sized RGD-Disintegrin obtained from Crotalus mictlantecuhtli venom, in vitro tested against human breast Cancer and endothelial cells","authors":"E. Rivas-Mercado , E. Neri-Castro , V. Zarzosa , L. Hernández-Orihuela , F. Olvera-Rodríguez , J.D. Torres-Garza , L. Garza-Ocañas","doi":"10.1016/j.tiv.2024.105987","DOIUrl":"10.1016/j.tiv.2024.105987","url":null,"abstract":"<div><div>Disintegrins are small non-enzymatic proteins present often at low concentration in the venom of viperid snakes. Isolated disintegrins are known for their lack of toxicity as well as their capacity to antagonize integrin receptors. Integrins are a major family of heterodimeric cell surface receptors that mediate cell-cell and cell-extracellular matrix (ECM) interactions. Integrins regulate key functions in cancer pathology and also tumor development. The aim of this study consisted in the isolation and characterization of disintegrins from rattlesnake new species <em>Crotalus mictlantecuhtli</em> venom. A disintegrin fraction obtained by RP-HPLC and named mictlan-D3, consist in two isoforms of 7439 and 7509 Da with 72 amino acid sequence containing the RGD binding motif. Mictlan-D3 inhibited MDA-MB-231 and HMEC-1 cell adhesion to laminin (LN), fibronectin (FN) and vitronectin (VN), highest inhibition was on MDA-MB-231 cell adhesion to LN by 81 % at 1 μM. The blockade of ⍺<sub>V</sub>β<sub>3</sub> integrin was evaluated by wound healing migration assay. Mictlan-D3 inhibited MDA-MB-231 cell migration by 80 % and 38 % after 24 and 72 h of incubation respectively. HMEC-1 cell migration was inhibited by 67.6 % and 27.9 % after 24 and 72 h of incubation. Additionally, mictlan-D3. This work represent the first characterization of disintegrins from the <em>Crotalus mictlantecuhtli</em> venom.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 105987"},"PeriodicalIF":2.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781347","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

Sinapic acid alleviates glutamate-induced excitotoxicity by inhibiting neuroinflammation and endoplasmic reticulum stress pathway in C6 glioma cells 辛酸通过抑制C6胶质瘤细胞的神经炎症和内质网应激途径减轻谷氨酸诱导的兴奋性毒性

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-28 DOI: 10.1016/j.tiv.2024.105977

Ahmet Mahmut Ortasoz , Ercan Ozdemir , Ahmet Sevki Taskıran , Aysegul Ozturk

{"title":"Sinapic acid alleviates glutamate-induced excitotoxicity by inhibiting neuroinflammation and endoplasmic reticulum stress pathway in C6 glioma cells","authors":"Ahmet Mahmut Ortasoz , Ercan Ozdemir , Ahmet Sevki Taskıran , Aysegul Ozturk","doi":"10.1016/j.tiv.2024.105977","DOIUrl":"10.1016/j.tiv.2024.105977","url":null,"abstract":"<div><div>Sinapic acid (SA) is a polyphenol compound derived from hydroxycinnamic acid found in various foods such as cereals and vegetables and has antioxidant, anti-inflammatory and neuroprotective properties. However, its effects on glutamate-induced excitotoxicity, which is important in neurodegenerative diseases, have not been fully elucidated. This study aimed to investigate the effect of SA on glutamate excitotoxicity and the possible role of proinflammatory cytokines and the endoplasmic reticulum (ER) stress pathway. In the study, C6 rat glioma cell line was used and the cells were divided into 4 groups: control, glutamate, SA and glutamate+SA. Cells were treated with 10 mM glutamate for 24 h to induce excitotoxicity. Additionally, SA was applied to cells at concentrations of 12.5 to 100 μM to examine its effects on glutamate excitotoxicity. XTT test was used for cell viability, and apoptotic cells were determined by immunofluorescence and flow cytometry methods. Proinflammatory cytokines (tumor necrosis factor-alpha, TNF-α and interleukin-beta, IL-1β), ER stress markers (glucose regulatory protein 78, GRP78; C/EBP homologous protein, CHOP and activating transcription factor-4, ATF-4) and caspase-3 was used to measure ELISA method. Findings indicated that SA (50 μM) significantly increased cell viability against glutamate-induced excitotoxicity (<em>p</em> < 0.05). Also, SA caused a significant decrease in TNF-α, IL-1β, GRP78, CHOP, ATF-4 and caspase-3 levels in glutamate-treated cells (<em>p</em> < 0.05). Flow cytometry and immunofluorescence staining results showed that SA reduced apoptosis in C6 glioma cells. In conclusion, our findings suggested that SA attenuated glutamate-induced excitotoxicity by preventing apoptosis through reducing proinflammatory cytokines and ER stress protein levels.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105977"},"PeriodicalIF":2.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757432","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

n-3 polyunsaturated fatty acids enhanced efficacy of cytarabine in iron-overloaded NALM-6 cells via apoptotic and oxidative pathways n-3多不饱和脂肪酸通过凋亡和氧化途径增强阿糖胞苷对铁超载NALM-6细胞的作用

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-28 DOI: 10.1016/j.tiv.2024.105976

Fatemeh Bahraini , Mahtab Sayadi , Hossein Safarpour , Asghar Zarban , Behzad Mesbahzadeh , Seyed Mehdi Sajjadi

{"title":"n-3 polyunsaturated fatty acids enhanced efficacy of cytarabine in iron-overloaded NALM-6 cells via apoptotic and oxidative pathways","authors":"Fatemeh Bahraini , Mahtab Sayadi , Hossein Safarpour , Asghar Zarban , Behzad Mesbahzadeh , Seyed Mehdi Sajjadi","doi":"10.1016/j.tiv.2024.105976","DOIUrl":"10.1016/j.tiv.2024.105976","url":null,"abstract":"<div><div>Despite progress in treating acute lymphoblastic leukemia (ALL), the adverse effects of chemotherapy toxicity and iron overload from transfusions continue to affect patients' quality of life. Polyunsaturated fatty acids (PUFAs) exhibit both antitumor and anti-inflammatory properties in leukemia. This study investigated the influence of n-3 PUFA on the efficacy of cytarabine in cells with iron overload. Iron overload was induced in NALM-6 cells using ferric ammonium citrate (FAC) and quantified through atomic absorption spectroscopy (AAS). The impact of n-3 PUFA on NALM-6 cells' response to cytarabine was evaluated using MTT, lactate dehydrogenase (LDH), apoptosis, and cell cycle assays. Additionally, gene expression analyses were performed on apoptotic, anti-apoptotic, and inflammatory genes, along with oxidative stress markers such as reactive oxygen species (ROS) and malondialdehyde (MDA) levels. The administration of n-3 PUFA significantly enhanced the effectiveness of cytarabine in iron-overloaded NALM-6 cells, leading to increased LDH secretion, elevated apoptosis rates, and G1 phase cell cycle arrest. These effects were associated with the upregulation of apoptotic genes such as P53 and caspase-8, the downregulation of the anti-apoptotic gene Bcl2, and a decrease in the inflammatory gene TNF-α. Furthermore, there was a notable increase in ROS and MDA levels. Overall, n-3 PUFA treatment improved cytarabine's efficacy in iron-overloaded NALM-6 cells by activating apoptotic processes and oxidative stress pathways.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105976"},"PeriodicalIF":2.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745163","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}

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