Toxicology in Vitro最新文献_第5页

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

Cytochrome P450-mediated metabolic interactions between donepezil and tadalafil in human liver microsomes 细胞色素 P450 介导的多奈哌齐和他达拉非在人类肝脏微粒体中的代谢相互作用。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-08-22 DOI: 10.1016/j.tiv.2024.105922

Jieun Yu , Ji Hyeon Ryu , Yong Ha Chi , Soo Heui Paik , Sang Kyum Kim

{"title":"Cytochrome P450-mediated metabolic interactions between donepezil and tadalafil in human liver microsomes","authors":"Jieun Yu , Ji Hyeon Ryu , Yong Ha Chi , Soo Heui Paik , Sang Kyum Kim","doi":"10.1016/j.tiv.2024.105922","DOIUrl":"10.1016/j.tiv.2024.105922","url":null,"abstract":"<div><p>Donepezil and tadalafil, commonly prescribed among older persons to treat dementia and erectile dysfunction, respectively, are primarily metabolized by cytochrome P450 (CYP) 3A4. However, the drug-drug interactions (DDIs) of these drugs are unknown. Therefore, this study evaluated the CYP-mediated metabolic interaction between donepezil and tadalafil using pooled human liver microsomes (HLMs) to predict their DDI potential. Donepezil metabolism was tadalafil-concentration dependently changed in HLMs incubated with 0.1 μM donepezil and showed the maximum 32.3% increase in the donepezil half-life at 1 μM tadalafil. The formation rates of donepezil metabolites, such as <em>N</em>-desbenzyl donepezil and 3-hydroxy donepezil, decreased by 28.3% and 30.3%, respectively, in HLMs incubated with 1 μM tadalafil and 0.1 μM donepezil. In contrast, neither the half-life of tadalafil nor the production rate of its metabolite, desmethylene tadalafil, was changed by >20% in the presence of donepezil (up to 1 μM). CYP3A4 activity was inhibited by tadalafil with an IC<sub>50</sub> value of 22.6 μM but not by donepezil. After pre-incubating HLMs with tadalafil and NADPH, the tadalafil IC<sub>50</sub> value against CYP3A4 was approximately 7.04-fold lower, suggesting time-dependent tadalafil inhibition. This study shows that the DDI between donepezil and tadalafil is primarily due to time-dependent inhibition against CYP3A4 by tadalafil.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105922"},"PeriodicalIF":2.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037681","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

Unveiling the anticancer potential of Pestalotioprolide E, an unexplored macrolide: Targeting TRXR1-TRX1-ASK1-P38 signaling cascade in triple-negative breast cancer 揭示大环内酯类药物 Pestalotioprolide E 的抗癌潜力：靶向三阴性乳腺癌的 TRXR1-TRX1-ASK1-P38 信号级联。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-08-22 DOI: 10.1016/j.tiv.2024.105920

Ruma Sarkar , Debobrata Paul , Akash Chatterjee , Anindita Bhattacharya , Sayantan Pradhan , Rajib Kumar Goswami , Prosenjit Sen

{"title":"Unveiling the anticancer potential of Pestalotioprolide E, an unexplored macrolide: Targeting TRXR1-TRX1-ASK1-P38 signaling cascade in triple-negative breast cancer","authors":"Ruma Sarkar , Debobrata Paul , Akash Chatterjee , Anindita Bhattacharya , Sayantan Pradhan , Rajib Kumar Goswami , Prosenjit Sen","doi":"10.1016/j.tiv.2024.105920","DOIUrl":"10.1016/j.tiv.2024.105920","url":null,"abstract":"<div><p>Triple-negative breast cancer (TNBC) is highly aggressive and metastatic in nature. Existing treatment modalities for TNBC are associated with severe side effects. Thioredoxin reductase (TRXR), the pivotal component of the thioredoxin system, remains overexpressed in various cancer cells including TNBC; promotes cell growth, proliferation, and metastasis, and inhibits apoptosis. Pestalotioprolide E is one of the potent macrolides, a class of secondary metabolites derived from an endophytic fungus <em>Pestalotiopsis microspora</em> with relatively unexplored biological activities. Our study revealed increased expression and activity of TRXR1 in MDA-MB-231 cells compared to the non-cancerous cells. In silico docking analysis and in vitro activity assay demonstrated that Pestalotioprolide E directly interacts with TRXR1 and inhibits its enzymatic activity. This inhibition induces apoptosis via TRX1/ASK1/P38MAPK death signaling cascade and retards metastasis through modulating VEGF, MMP-2, MMP-9, E-cadherin, N-cadherin in MDA-MB-231 cells. Taken together present study establishes TRXR1 as a molecular target for Pestalotioprolide E and its anticancer effect can be attributed to the inhibition of TRXR1 activity in MDA-MB-231.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105920"},"PeriodicalIF":2.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037682","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

Silencing Nrf2 in cisplatin resistant non-small cell lung cancer cells augments sensitivity towards EGFR inhibitor 在顺铂耐药的非小细胞肺癌细胞中抑制 Nrf2 可提高对表皮生长因子受体抑制剂的敏感性。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-08-22 DOI: 10.1016/j.tiv.2024.105921

Chandrani Fouzder , Alpana Mukhuty , Dipanjan Chattopadhyay , Snehasis Das , Sumit Kumar Hira , Rakesh Kundu

{"title":"Silencing Nrf2 in cisplatin resistant non-small cell lung cancer cells augments sensitivity towards EGFR inhibitor","authors":"Chandrani Fouzder , Alpana Mukhuty , Dipanjan Chattopadhyay , Snehasis Das , Sumit Kumar Hira , Rakesh Kundu","doi":"10.1016/j.tiv.2024.105921","DOIUrl":"10.1016/j.tiv.2024.105921","url":null,"abstract":"<div><p>Recently, non-small cell lung cancer (NSCLC) has been the prime concern of cancer clinicians due to its high mortality rate worldwide. Cisplatin, a platinum derivative, has been used as a therapeutic option for treating metastatic NSCLC for several years. However, acquired, or intrinsic drug resistance to Cisplatin is the major obstacle to the successful treatment outcome of patients. Dysregulation of Nrf2 (nuclear factor erythroid 2-related factor 2) and EGFR (epidermal growth factor receptor) signaling have been associated with cellular proliferation, cancer initiation, progression and confer drug resistance to several therapeutic agents including Cisplatin in various cancers. To dissect the molecular mechanism of EGFR activation in resistant cells, we developed Cisplatin-resistant (CisR) human NSCLC cell lines (A549 and NCIH460) with increasing doses of Cisplatin treatment over a 3-month period. CisR cells demonstrated increased proliferative capacity, clonogenic survivability and drug efflux activity compared to the untreated parental (PT) cells. These resistant cells also showed higher levels of Nrf2 and EGFR expression. Here, we found that Nrf2 upregulates both basal and inducible expression of EGFR in these CisR cells at the transcriptional level. Moreover, genetic inhibition of Nrf2 with siRNA in CisR cells showed increased sensitivity towards the EGFR tyrosine kinase inhibitor (TKIs), AG1478. Our study, therefore suggests the use of Nrf2 inhibitors in combinatorial therapy with EGFR TKIs for the treatment of resistant NSCLC.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105921"},"PeriodicalIF":2.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047535","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

Isobavachin induces autophagy-mediated cytotoxicity in AML12 cells via AMPK and PI3K/Akt/mTOR pathways 异巴伐醌通过AMPK和PI3K/Akt/mTOR途径诱导AML12细胞自噬介导的细胞毒性。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-08-16 DOI: 10.1016/j.tiv.2024.105919

Ning Xia , Qing-Hai Chen , Zhao-Jun Meng , Shu-Yue Ma , Jia-Li Huang , Rong Shen , Yu-Tong Dong , Hai-Wei Du , Kun Zhou

{"title":"Isobavachin induces autophagy-mediated cytotoxicity in AML12 cells via AMPK and PI3K/Akt/mTOR pathways","authors":"Ning Xia , Qing-Hai Chen , Zhao-Jun Meng , Shu-Yue Ma , Jia-Li Huang , Rong Shen , Yu-Tong Dong , Hai-Wei Du , Kun Zhou","doi":"10.1016/j.tiv.2024.105919","DOIUrl":"10.1016/j.tiv.2024.105919","url":null,"abstract":"<div><p>Isobavachin (IBA) is a dihydroflavonoid compound with various pharmacological effects. However, further investigation into the hepatotoxicity of IBA is necessary. This study aims to identify the hepatotoxic effects of IBA and explore its potential mechanisms. The study assessed the impact of IBA on the viability of AML12, HepG2, LO2, rat, and mouse primary hepatocytes using MTT and LDH assays. Autophagy was detected in AML12 cells after IBA treatment using electron microscopy, MDC, and Ad-mCherry-GFP-LC3B fluorescence. The effect of IBA on autophagy-related proteins was examined using Western blot. The results showed that IBA had dose-dependent inhibitory effects on five cells, induced autophagy in AML12 cells, and promoted autophagic flux. The study found that IBA treatment inhibited phosphorylation of PI3K, Akt, and mTOR, while increasing phosphorylation levels of AMPK and ULK1. Treatment with both AMPK and PI3K inhibitors reversed the expression of AMPK and PI3K-Akt-mTOR signaling pathway proteins. These results suggest that IBA may have hepatocytotoxic effects but can also prevent IBA hepatotoxicity by inhibiting the AMPK and PI3K/Akt/mTOR signaling pathways. This provides a theoretical basis for preventing and treating IBA hepatotoxicity in clinical settings.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105919"},"PeriodicalIF":2.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001366","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

Ex vivo skin diffusion and decontamination studies of titanium dioxide nanoparticles 二氧化钛纳米粒子的体外皮肤扩散和净化研究。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-08-13 DOI: 10.1016/j.tiv.2024.105918

Adeline Tarantini , Emilie Jamet-Anselme , Sabine Lam , Vincent Haute , David Suhard , Nathalie Valle , Véronique Chamel-Mossuz , Céline Bouvier-Capely , Guillaume Phan

{"title":"Ex vivo skin diffusion and decontamination studies of titanium dioxide nanoparticles","authors":"Adeline Tarantini , Emilie Jamet-Anselme , Sabine Lam , Vincent Haute , David Suhard , Nathalie Valle , Véronique Chamel-Mossuz , Céline Bouvier-Capely , Guillaume Phan","doi":"10.1016/j.tiv.2024.105918","DOIUrl":"10.1016/j.tiv.2024.105918","url":null,"abstract":"<div><p>This study aims to adapt an experimental model based on Franz diffusion cells and porcine skin explants to characterize the diffusion of TiO<sub>2</sub> NPs and to compare the efficacy of different cleansing products, soapy water and a calixarene cleansing nanoemulsion compared with pure water, as a function of the time of treatment.</p><p>While TiO<sub>2</sub> NPs tend to form agglomerates in aqueous solutions, a diffusion through healthy skin was confirmed as particles were detected in the receptor fluid of Franz cells using sp-ICP-MS. In the absence of treatment, SIMS images showed the accumulation of TiO<sub>2</sub> agglomerates in the stratum corneum, the epidermis, the dermis, and around hair follicles. Decontamination assays showed that the two products tested were comparably effective in limiting Ti penetration, whatever the treatment time. However, only calixarene nanoemulsion was statistically more efficient than water in retaining TiO<sub>2</sub> in the donor compartment (>89%), limiting retention inside the skin (<1%) and preventing NP diffusion through the skin (<0.13%) when treatments were initiated 30 min after skin exposure. When decontamination was delayed from 30 min to 6 h, the amount of Ti diffusing and retained in the skin increased.</p><p>This study demonstrates that TiO<sub>2</sub> NPs may diffuse through healthy skin after exposure. Thus, effective decontamination using cleansing products should be carried out as soon as possible.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105918"},"PeriodicalIF":2.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887233324001486/pdfft?md5=a95e59abe87f08a278679b370946f8f8&pid=1-s2.0-S0887233324001486-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983975","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

Photodynamic therapy with curcumin and near-infrared radiation as an antitumor strategy to glioblastoma cells 利用姜黄素和近红外辐射的光动力疗法作为胶质母细胞瘤细胞的抗肿瘤策略。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-08-12 DOI: 10.1016/j.tiv.2024.105917

Marcelo Augusto Germani Marinho , Magno da Silva Marques , Camila de Oliveira Vian , Daza de Moraes Vaz Batista Filgueira , Ana Paula Horn

{"title":"Photodynamic therapy with curcumin and near-infrared radiation as an antitumor strategy to glioblastoma cells","authors":"Marcelo Augusto Germani Marinho , Magno da Silva Marques , Camila de Oliveira Vian , Daza de Moraes Vaz Batista Filgueira , Ana Paula Horn","doi":"10.1016/j.tiv.2024.105917","DOIUrl":"10.1016/j.tiv.2024.105917","url":null,"abstract":"<div><p>Glioblastoma is a malignant neoplasm that develops in the central nervous system and is characterized by high rates of cell proliferation and invasion, presenting resistance to treatments and a poor prognosis. Photodynamic therapy (PDT) is a therapeutic modality that can be applied in oncological cases and stands out for being less invasive. Photosensitizers (PS) of natural origin gained prominence in PDT. Curcumin (CUR) is a natural compound that has been used in PDT, considered a promising PS. In this work, we evaluated the effects of PDT-mediated CUR and near-infrared radiation (NIR) in glioblastoma cells. Through trypan blue exclusion analysis, we chose the concentration of 5 μM of CUR and the dose of 2 J/cm<sup>2</sup> of NIR that showed better responses in reducing the viable cell number in the C6 cell line and did not show cytotoxic/cytostatic effects in the HaCat cell line. Our results show that there is a positive interaction between CUR and NIR as a PDT model since there was an increase in ROS levels, a decrease in cell proliferation, increase in cytotoxicity with cell death by autophagy and necrosis, in addition to the presence of oxidative damage to proteins. These results suggest that the use of CUR and NIR is a promising strategy for the antitumor application of PDT.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105917"},"PeriodicalIF":2.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983976","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

Involvement of Sirt1-FoxO3a-Bnip3 axis and autophagy mediated mitochondrial turnover in according protection to hyperglycemic NRK-52E cells by Berberine Sirt1-FoxO3a-Bnip3 轴和自噬介导的线粒体转换参与了小檗碱对高血糖 NRK-52E 细胞的保护。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-08-08 DOI: 10.1016/j.tiv.2024.105916

Sugandh Saxena , Sumit Kumar Anand , Ankita Sharma , Poonam Kakkar

{"title":"Involvement of Sirt1-FoxO3a-Bnip3 axis and autophagy mediated mitochondrial turnover in according protection to hyperglycemic NRK-52E cells by Berberine","authors":"Sugandh Saxena , Sumit Kumar Anand , Ankita Sharma , Poonam Kakkar","doi":"10.1016/j.tiv.2024.105916","DOIUrl":"10.1016/j.tiv.2024.105916","url":null,"abstract":"<div><p>Aberrant accumulation of dysfunctional mitochondria in renal cells during hyperglycemia signifies perturbed autophagy and mitochondrial turnover. This study aims to focus on the underlying mechanism involved in autophagy and mitophagy inducing efficacy of Berberine (isoquinoline alkaloid) in hyperglycemic NRK-52E cells. Berberine mediated protection to hyperglycemic cells prevented alteration in mitochondrial structure and function. Treatment with SRT-1720 (Sirt1 activator) enhanced autophagy, decreased apoptosis, upregulated expression of downstream moieties (FoxO3a and Bnip3) and ameliorated mitochondria related anomalies while nicotinamide (Sirt1 inhibitor) treatment exhibited reversal of the same. GFP reporter assay ascertained enhanced transcriptional activity of FoxO in Berberine-treated hyperglycemic cells, which was found to be correlated to increased expression of downstream protein Bnip3. Knocking down FoxO3a disrupted autophagy and stimulated apoptosis. <em>N</em>-acetyl-L-cysteine pre-treatment confirmed that generation of ROS intervened high glucose induced toxicity in NRK-52E cells. Berberine co-treatment resulted in differential expressions of key proteins involved in autophagy and mitophagy like LC3B, ATGs, Beclin1, Sirt1, Bnip3, FoxO3a and Parkin. Further, enhanced mitophagy in Berberine-treated cells was confirmed by transmission electron microscopy. Thus, our findings give evidence that the protection accorded by Berberine against hyperglycemia in renal proximal tubular cells (NRK-52E) involves instigation of Sirt1-FoxO3a-Bnip3 axis and autophagy mediated mitophagy induction.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105916"},"PeriodicalIF":2.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro impacts of polystyrene microplastics and environmental pollutants on ethoxyresorufin-O-deethylase and glutathione S-transferase activity in Mossambica tilapia 聚苯乙烯微塑料和环境污染物对罗非鱼乙氧苏鲁素-O-脱乙基酶和谷胱甘肽 S-转移酶活性的体外影响。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-08-05 DOI: 10.1016/j.tiv.2024.105915

Yan Yin , Haiyan Wang , Guijing Ouyang , Daxiong Han

{"title":"In vitro impacts of polystyrene microplastics and environmental pollutants on ethoxyresorufin-O-deethylase and glutathione S-transferase activity in Mossambica tilapia","authors":"Yan Yin , Haiyan Wang , Guijing Ouyang , Daxiong Han","doi":"10.1016/j.tiv.2024.105915","DOIUrl":"10.1016/j.tiv.2024.105915","url":null,"abstract":"<div><p>Microplastic (MP) pollution is a potential threat to marine organisms. <em>In vitro</em> toxicity of MPs and other pollutants, such as pharmaceutically active compounds (PhACs) and brominated flame retardants (BFRs), has been understudied. This study aimed to investigate the effects of polystyrene microplastics (PS-MPs) with different particle sizes on two biomarkers: ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) in tilapia liver homogenates. The study also examined the combined effects of PS-MPs with various environmental contaminants, including three metal ions (Cu<sup>2+</sup>, Zn<sup>2+</sup>, Pb<sup>2+</sup>), three BFRs, and six PhACs. PS-MPs alone had no remarkable effects on the two biomarkers at the selected concentrations. However, PS-MPs combined with other pollutants significantly affected the two biomarkers in most situations. For EROD activity, PS + metal ions (except Zn<sup>2+</sup> at 1000 μg/L), PS + BFRs (except decabromodiphenyl oxide (BDE-209)) or PS+ trimethoprim (TMP) significantly inhibited activity values, whereas PS+ 4-acetaminophen (AMP) induced EROD activity. For GST, PS together with most tested pollutants (except PS+ ibuprofen (IBF)) greatly decreased the activities. Accordingly, future research should focus on combined toxicity of mixtures to set more reasonable environmental safety evaluation standards.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105915"},"PeriodicalIF":2.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903606","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

Estrogen receptor/androgen receptor transcriptional activation of benzophenone derivatives and integrated approaches to testing and assessment (IATA) for estrogenic effects 二苯甲酮衍生物的雌激素受体/雄激素受体转录激活以及雌激素效应测试和评估综合方法（IATA）。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-07-31 DOI: 10.1016/j.tiv.2024.105914

Handule Lee, Juyoung Park, Darlene M. Ortiz, Kwangsik Park

{"title":"Estrogen receptor/androgen receptor transcriptional activation of benzophenone derivatives and integrated approaches to testing and assessment (IATA) for estrogenic effects","authors":"Handule Lee, Juyoung Park, Darlene M. Ortiz, Kwangsik Park","doi":"10.1016/j.tiv.2024.105914","DOIUrl":"10.1016/j.tiv.2024.105914","url":null,"abstract":"<div><p>Estrogen receptor (ER) and androgen receptor (AR) transactivation assays for the benzophenone compounds (BPs) were performed using hERα-HeLa-9903 cells for ER and MMTV/22Rv1_GR-KO cells for AR. Results showed that some BPs, such as BP-1, BP-2, 4OH-BP, 4DHB, and 4-MBP, showed agonistic activity on ER with a higher RPCmax than 1 nM 17-β estradiol. The other BPs (BP, BP-3, BP-6, BP-7, and BP-8) showed low RPCmax in accordance with the OECD Test guideline (TG) 455 criteria, with BP-4 as the only ER-negative. However, the potency of the BPs was at least 1000 times less than the reference chemical, 17-β-estradiol. None of the BPs exhibited agonistic activity on AR except BP-2 which showed a small increase in activity. For further evaluation of the estrogenic effect of BPs based on the integrated approaches to testing and assessment (IATA) approach, existing data on ER binding, steroidogenesis, MCF-7 cell proliferation, and <em>in vivo</em> uterotrophic assays were collected and evaluated. There seemed to be a close association between the <em>in vitro</em> data on BPs, especially ER transcriptional activity, and the <em>in vivo</em> results of increased uterine weight. This case study implied that integrated approaches using <em>in vitro</em> data can be a useful tool for the prediction of <em>in vivo</em> data for estrogenic effects, without the need for additional animal toxicity tests.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105914"},"PeriodicalIF":2.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879811","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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