Toxicology letters最新文献

筛选
英文 中文
ARC protects cochlear hair cells from neomycin-induced ototoxicity via the Ras/JNK signaling pathway ARC 通过 Ras/JNK 信号通路保护耳蜗毛细胞免受新霉素诱导的耳毒性影响。
IF 2.9 3区 医学
Toxicology letters Pub Date : 2025-01-01 DOI: 10.1016/j.toxlet.2024.12.005
Xiaoyu Yu , Hanbing Gao , Jie Zhang , Qiaojun Fang , Wenjie Kang , Haiqiong Shang , Xiangyu Lou , Ming Guan
{"title":"ARC protects cochlear hair cells from neomycin-induced ototoxicity via the Ras/JNK signaling pathway","authors":"Xiaoyu Yu ,&nbsp;Hanbing Gao ,&nbsp;Jie Zhang ,&nbsp;Qiaojun Fang ,&nbsp;Wenjie Kang ,&nbsp;Haiqiong Shang ,&nbsp;Xiangyu Lou ,&nbsp;Ming Guan","doi":"10.1016/j.toxlet.2024.12.005","DOIUrl":"10.1016/j.toxlet.2024.12.005","url":null,"abstract":"<div><div>The present study was designed to investigate the role and mechanism of the Apoptosis repressor with caspase recruitment domain (ARC) in protecting the neomycin-induced hair cell damage. HEI-OC1 cells and basilar membrane culture were applied to determine the effect of ARC. Plasmid transfection was used to regulate the ARC or Ras expression. We have found the ARC overexpression in HEI-OC1 cells can increase the cell viability and decrease cell apoptosis after neomycin injury. The cleaved caspase 3 was reduced in ARC overexpression group after neomycin treatment. The p-CREB expression was increased in ARC overexpression group, while the p-c-Jun expression was decreased after neomycin incubation. In HEI-OC1 cells and basilar membranes, JNK and Ras inhibitions both can reduce ARC expression, and Ras overexpression can increase the ARC expression. This study indicates that ARC can protect the hair cells from neomycin-induced apoptosis through Ras/JNK signaling pathway. Our findings provide new insights in preventing cochlear HC death after drug-induced ototoxicity.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 111-119"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819332","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
Early developmental effects of propofol exposure in different stages of zebrafish embryos 异丙酚暴露对斑马鱼胚胎不同阶段的早期发育影响。
IF 2.9 3区 医学
Toxicology letters Pub Date : 2025-01-01 DOI: 10.1016/j.toxlet.2024.12.002
Luís Félix , Sónia Campos , Paula Guedes de Pinho , Luís Antunes , Ana M. Valentim
{"title":"Early developmental effects of propofol exposure in different stages of zebrafish embryos","authors":"Luís Félix ,&nbsp;Sónia Campos ,&nbsp;Paula Guedes de Pinho ,&nbsp;Luís Antunes ,&nbsp;Ana M. Valentim","doi":"10.1016/j.toxlet.2024.12.002","DOIUrl":"10.1016/j.toxlet.2024.12.002","url":null,"abstract":"<div><div>The mechanism of action of propofol, a common intravenous anaesthetic, in early life stages is not well understood with contradictory studies showing neurotoxic and neurogenic effects in the developing brain. Zebrafish early life stages have been established as an alternative model for animal experimentation with propofol toxicological effects reported following chronic exposure. Yet, the acute exposure to other anaesthetics has been shown to induce early life stage-dependent toxicological outcomes. Therefore, the present study aimed to evaluate the teratogenic effects of propofol at the 256-cell, 50 % epiboly and 1–4 somite stages following a 20 min exposure. Embryos were exposed after primarily assessment of propofol acute toxicity (24h-LC<sub>50</sub>=9.82 μg mL<sup>−1</sup>) and absorption at different developmental stages by chromatography. Embryos (2 hours post-fertilization, hpf) were treated with an anaesthetic and toxicological concentration of propofol (2.5 and 10 μg mL<sup>−1</sup>, respectively) for 20-min. Mortality and developmental toxicity were then evaluated until 144 hpf, when the behaviour and oxidative-stress-related biomarkers were assessed. Exposure at the 256-cell stage resulted in a concentration-dependent increased number of abnormalities in head, fins and tail and a decreased body length as well as in changes in ATPase activity for the lowest concentration. On the other hand, exposure at later stages resulted in a decreased survival while no significant malformations were detected. Yet, exposure during the 50 % epiboly stage resulted in the increase of ROS levels as well as glutathione (GST and GSSG) levels while exposure at 1–4 somite stage resulted in increased DNA damage and ATPase alterations. The behaviour of zebrafish was similar among treatments. Overall, these findings show highlight the stage-dependent teratogenic potential of short propofol exposures during zebrafish early development. The alterations observed may be linked to the activation of the zygotic transcription in embryos, requiring further studies to delve into the molecular changes underlying the observed effects.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 84-93"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795148","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
Introducing the OECD guidance document on occupational biomonitoring: A harmonized methodology for deriving occupational biomonitoring levels (OBL) 介绍OECD关于职业生物监测的指导文件:获得职业生物监测水平(OBL)的统一方法。
IF 2.9 3区 医学
Toxicology letters Pub Date : 2025-01-01 DOI: 10.1016/j.toxlet.2024.12.006
Nancy B. Hopf , Jos Bessems , Tiina Santonen , Susana Viegas , Ludwine Casteleyn , Devika Poddalgoda , Farida Lamkarkach , Thomas Göen , Maryam Zare Jeddi , Michael Koller , Christophe Rousselle , Kate Jones , Kaspar Schmid , Rex FitzGerald , Michael Bader , Koki Takaki , Patience Browne , Virpi Väänänen , Radu Corneliu Duca , Robert Pasanen-Kase
{"title":"Introducing the OECD guidance document on occupational biomonitoring: A harmonized methodology for deriving occupational biomonitoring levels (OBL)","authors":"Nancy B. Hopf ,&nbsp;Jos Bessems ,&nbsp;Tiina Santonen ,&nbsp;Susana Viegas ,&nbsp;Ludwine Casteleyn ,&nbsp;Devika Poddalgoda ,&nbsp;Farida Lamkarkach ,&nbsp;Thomas Göen ,&nbsp;Maryam Zare Jeddi ,&nbsp;Michael Koller ,&nbsp;Christophe Rousselle ,&nbsp;Kate Jones ,&nbsp;Kaspar Schmid ,&nbsp;Rex FitzGerald ,&nbsp;Michael Bader ,&nbsp;Koki Takaki ,&nbsp;Patience Browne ,&nbsp;Virpi Väänänen ,&nbsp;Radu Corneliu Duca ,&nbsp;Robert Pasanen-Kase","doi":"10.1016/j.toxlet.2024.12.006","DOIUrl":"10.1016/j.toxlet.2024.12.006","url":null,"abstract":"<div><div>Derivation of occupational biomonitoring levels (OBLs) is needed to effectively utilize biomonitoring for assessing exposures to chemical substances, and consequently, implement risk reduction measures to reduce health risks among workers. OBLs are the appropriate option for chemical substances that can be absorbed through the skin. This methodology for derivation of OBLs has been developed in collaboration with scientific and regulatory experts from more than 40 institutes in 15 countries within the Organization for Economic Cooperation and Development (OECD) framework. This manuscript provides a summary of the guidance on derivation of OBLs destined for scientists, risk assessors, and regulators who are tasked with establishing OBLs for regulatory purposes and implementing occupational biomonitoring programs. The derivation methodology follows a tiered approach based on the strength of evidence and quality of the data that we have labeled level of confidence. The tiered approach serves as a practical framework in occupational health risk assessment and management. We distinguish between four OBL levels depending on the strength of scientific evidence and confidence level: health-based derivation of OBL based on robust epidemiological data showing causal exposure-health effect relationship and Provisional OBL (POBL) based on robust toxicological animal data showing dose-response relationship as well as two assessment values which are not health based: reference levels in the general population (Reference OBL or (ROBL)), and Technical achievable OBL or (TOBL). Four case studies illustrating the derivation methods for OBLs and POBLs are also provided. Using this state-of-the-art approach (OECD guidance document no. 370) will lead to a harmonized derivation of OBLs and subsequently to evidence-based risk management measures.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 132-143"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839769","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
N6-methyladenosine mediated-NRF2 signaling pathway attenuates cadmium cytotoxicity by inhibiting oxidative damage in bronchial epithelial cells n6 -甲基腺苷介导的nrf2信号通路通过抑制支气管上皮细胞氧化损伤来减弱镉的细胞毒性。
IF 2.9 3区 医学
Toxicology letters Pub Date : 2025-01-01 DOI: 10.1016/j.toxlet.2024.12.007
Nan Zhang , Yuan Zhao , Jie Yang , Yifei Sun , Rongxian Li , Zuoshun He , Shiyan Gu
{"title":"N6-methyladenosine mediated-NRF2 signaling pathway attenuates cadmium cytotoxicity by inhibiting oxidative damage in bronchial epithelial cells","authors":"Nan Zhang ,&nbsp;Yuan Zhao ,&nbsp;Jie Yang ,&nbsp;Yifei Sun ,&nbsp;Rongxian Li ,&nbsp;Zuoshun He ,&nbsp;Shiyan Gu","doi":"10.1016/j.toxlet.2024.12.007","DOIUrl":"10.1016/j.toxlet.2024.12.007","url":null,"abstract":"<div><div>Although N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) and its regulatory proteins were involved in multiple cellular damage processes, the roles of m<sup>6</sup>A and its regulatory proteins in cadmium-induced pulmonary cell damage remain largely unknown. Our present data indicated that cadmium exposure caused serious damage in bronchial epithelial cells, as evidenced by reduction of cell viability and elevation of oxidative damage and apoptosis. These processes were accompanied by alterations of m<sup>6</sup>A modification and its regulatory proteins (FTO, ALKBH5, YTHDC2). It is noteworthy that pretreatment with the m<sup>6</sup>A agonist entacapone (ENT) markedly attenuated the detrimental effects of cadmium, including cell death, oxidative damage, and the activation of the nuclear factor erythroid 2-related factor 2 (NRF2)signalling pathway. Conversely, the detrimental effects of CdSO<sub>4</sub> were significantly exacerbated when m<sup>6</sup>A levels were inhibited by 3-deazidyladenosine (DAA). Further prediction result revealed that multiple m<sup>6</sup>A-modified sites occur on <em>NRF2</em> mRNA with high confidence level, implicating that m<sup>6</sup>A modification on <em>NRF2</em> mRNA may affect the protein expression of NRF2. In conclusion, our data together suggest that m<sup>6</sup>A modification play critical roles in cadmium-induced bronchial epithelial cell damage, during which NRF2 signaling pathway may act as an important bridge for m<sup>6</sup>A modification to regulate cellular damage. This study offer a promising avenue for further investigation into the mechanisms underlying cadmium-induced bronchial epithelial cell damage from the perspective of RNA epigenetics.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 144-158"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898339","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
Oxymatrine antagonises oxidative stress and apoptosis in Nemopilema nomurai toxin-induced cardiotoxicity by inhibiting mitogen-activated protein kinase 氧化苦参碱通过抑制丝裂原活化蛋白激酶,拮抗尼莫梭菌毒素诱导的心脏毒性中的氧化应激和细胞凋亡。
IF 2.9 3区 医学
Toxicology letters Pub Date : 2025-01-01 DOI: 10.1016/j.toxlet.2024.12.004
Xinming Wang , Yongfang Wang , Xiaoyu Geng , Zengfa Wang , Jinyu Zhang , Tianwen Liu , Wei Chen , Jishun Yang , Liang Xiao , Weibing Dong
{"title":"Oxymatrine antagonises oxidative stress and apoptosis in Nemopilema nomurai toxin-induced cardiotoxicity by inhibiting mitogen-activated protein kinase","authors":"Xinming Wang ,&nbsp;Yongfang Wang ,&nbsp;Xiaoyu Geng ,&nbsp;Zengfa Wang ,&nbsp;Jinyu Zhang ,&nbsp;Tianwen Liu ,&nbsp;Wei Chen ,&nbsp;Jishun Yang ,&nbsp;Liang Xiao ,&nbsp;Weibing Dong","doi":"10.1016/j.toxlet.2024.12.004","DOIUrl":"10.1016/j.toxlet.2024.12.004","url":null,"abstract":"<div><div>Jellyfish stings can trigger abrupt heart failure via toxins, leading acute mortality rise. Proposed mechanisms involve oxidative stress and apoptosis, but evidence for effective treatments is lacking. To explore the concrete molecular mechanisms of jellyfish toxin-induced cardiotoxicity and to explore effective therapeutic approaches, we established tentacle extract (TE) of jellyfish <em>Nemopilema nomurai</em> induced cardiotoxicity models in vivo and in vitro based Intelligent Character Recognition (ICR) mice and H9C2 cells, respectively,.We assessed toxin-induced cardiac injury and screened antagonists from natural compounds to evaluate their antagonistic effects and explore their mechanisms of action. In vitro experiments showed that TE reduced the viability of H9C2 cells and induced a large number of cells apoptotic, accompanied by the elevation of reactive oxygen species (ROS), malondialdehyde (MDA) and the decrease of total superoxide dismutase (T-SOD), activated the phosphorylation level of mitogen-activated protein kinase (MAPK) nuclear transcription factors p38, extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase (JNK), and increased the transcription level of upstream cytokines interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), and OMT can significantly antagonize the above changes caused by TE; in vivo experiments demonstrated that TE could lead to the death of mice, as well as induce cardiac edema and rupture of myocardial fibers. In contrast, Oxymatrine (OMT) effectively counteracts the lethal effects of TE and reduces both cardiac edema and myocardial fiber rupture. In summary, OMT can antagonise TE-induced cardiac injury and lethal effects by inhibiting the activation of the MAPK pathway and reducing oxidative stress and apoptosis. As a natural compound, OMT offers a potential therapeutic strategy for jellyfish stings.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 120-131"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822601","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 and validation of a multicompound LLE–LC–MS/MS method for biomonitoring of hazardous medicinal products in urine of exposed workers 多化合物液相色谱-液相色谱-质谱联用/质谱联用方法对暴露工人尿液中有害药品进行生物监测的建立与验证。
IF 2.9 3区 医学
Toxicology letters Pub Date : 2025-01-01 DOI: 10.1016/j.toxlet.2024.11.012
Maria Francisca Portilha-Cunha , Arminda Alves , Ana R.L. Ribeiro , Adrián M.T. Silva , Pedro Norton , Mónica S.F. Santos
{"title":"Development and validation of a multicompound LLE–LC–MS/MS method for biomonitoring of hazardous medicinal products in urine of exposed workers","authors":"Maria Francisca Portilha-Cunha ,&nbsp;Arminda Alves ,&nbsp;Ana R.L. Ribeiro ,&nbsp;Adrián M.T. Silva ,&nbsp;Pedro Norton ,&nbsp;Mónica S.F. Santos","doi":"10.1016/j.toxlet.2024.11.012","DOIUrl":"10.1016/j.toxlet.2024.11.012","url":null,"abstract":"<div><div>Antineoplastic drugs are carcinogens, mutagens, or teratogenic substances, which can pose serious risks to professionals. Concerns about chronic exposure to these hazardous medicinal products (HMPs) have led to their prominence in the EU strategic framework on health and safety at work 2021–2027. To estimate and mitigate human exposure to HMPs, regular monitoring programs and, consequently, reliable, sensitive, multicomponent methods are crucial. In this study, an unconventional liquid-liquid extraction coupled with liquid chromatography–tandem mass spectrometry analysis is proposed to simultaneously identify and quantify seven HMPs of high concern in urine: cyclophosphamide, etoposide, ifosfamide, paclitaxel, megestrol, mycophenolate mofetil, and tamoxifen, the last three for the first time. Recoveries of all drugs from urine samples were close to 100 %, and method detection limits (0.6–4.1 ng/L) were noticeably lower than most previously reported. This novel, non-invasive method for biomonitoring is thus suitable to unequivocally identify the target drugs at the expected trace levels in urine and to infer about workers' exposure. The method contributes to the conception of regular monitoring programs for antineoplastic drugs, in line with recommendations under EU Directive 2004/37/EC. This is especially relevant in Portugal, where neither analytical methods nor exposure data exist due to lack of formal surveillance.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 40-49"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772601","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
Effects of short-term exposure to printing shop particles on inflammatory responses and DNA damage in healthy young adults 短期暴露于打印车间颗粒对健康年轻人炎症反应和DNA损伤的影响
IF 2.9 3区 医学
Toxicology letters Pub Date : 2025-01-01 DOI: 10.1016/j.toxlet.2024.12.001
Hongbo Wang , Lizhi Lyu , Zheyu Huang , Yu Xu , Langzhi He , Zihui Li , Chen Li , Hasenbilige , Jiajing Zhou , Yun Wang
{"title":"Effects of short-term exposure to printing shop particles on inflammatory responses and DNA damage in healthy young adults","authors":"Hongbo Wang ,&nbsp;Lizhi Lyu ,&nbsp;Zheyu Huang ,&nbsp;Yu Xu ,&nbsp;Langzhi He ,&nbsp;Zihui Li ,&nbsp;Chen Li ,&nbsp;Hasenbilige ,&nbsp;Jiajing Zhou ,&nbsp;Yun Wang","doi":"10.1016/j.toxlet.2024.12.001","DOIUrl":"10.1016/j.toxlet.2024.12.001","url":null,"abstract":"<div><div>Considering the increasingly demand for printing in daily life, more attention should be paid to the health risks of printer emissions to consumers. This study designed a two-stage cross-over study with 20 volunteers to investigate whether the short-term exposure to printing shop particles (PSPs) could cause inflammatory responses and genetic damage in healthy young volunteers. According to the study, short-term exposure to high level of PSPs caused the elevation of eotaxin and TNF-α levels in serum, indicating PSPs exposure led to the inflammation in healthy subjects. However, no significant changes of the urine 8-OH-dG was observed after PSPs exposure and there was no significant difference of micronucleus frequency in peripheral blood lymphocytes of volunteers between the high-exposure-level and low-exposure-level period. Our study suggested that short-term exposure to high level of PSPs could cause mild inflammatory responses but no DNA damage in healthy subjects. More attention should be paid to the health hazards of the regular use of laser printers in daily life.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 105-110"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787114","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
High glucose enhances malignant progression of MDA-MB-231 cells through cumulative effect 高糖通过累积效应促进MDA-MB-231细胞的恶性进展。
IF 2.9 3区 医学
Toxicology letters Pub Date : 2025-01-01 DOI: 10.1016/j.toxlet.2024.11.008
Gaotao Zhang , Zhiqin Liu , Huixin Zheng , Yuanzhuang Xu , Donghao Zhang , Queting Chen , Duqiang Luo
{"title":"High glucose enhances malignant progression of MDA-MB-231 cells through cumulative effect","authors":"Gaotao Zhang ,&nbsp;Zhiqin Liu ,&nbsp;Huixin Zheng ,&nbsp;Yuanzhuang Xu ,&nbsp;Donghao Zhang ,&nbsp;Queting Chen ,&nbsp;Duqiang Luo","doi":"10.1016/j.toxlet.2024.11.008","DOIUrl":"10.1016/j.toxlet.2024.11.008","url":null,"abstract":"<div><div>Previous investigations have shown that high glucose can promote breast cancer progression. However, the relationship between high glucose microenvironment and triple-negative breast cancer (TNBC) remains to be explored. In this study, we performed RNA-seq to explore the effect of short-term high glucose and long-term high glucose on MDA-MB-231 cell line. A total of 896 highly ranked differentially expressed genes (DEGs) were identified, including 57 DEGs of short-term high glucose group and 839 DEGs of long-term high glucose group. The DEGs of short-term high glucose group were mainly associated with IL-17 signaling pathway. Nonetheless, the DEGs of long-term high glucose group were primarily involved in IL-17 signaling pathway, MAPK signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Toll-like receptor signaling pathway, and VEGF signaling pathway. Additionally, 8 hub genes of short-term high glucose group were enriched in metabolic pathway. Moreover, 10 hub genes of long-term high glucose group were enriched in ribosome pathway. Subsequently, <em>in vitro</em> experiment results found that high glucose can promote cell proliferation, and has a time accumulation effect. In addition, high glucose can induce the accumulation of inflammatory factors and promote angiogenesis. Collectively, these findings provide novel insights into the effect of diabetes mellitus type 2 (T2DM) on TNBC.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 17-31"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755572","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
An overview of immunotoxicity in drug discovery and development 药物研发中的免疫毒性概述。
IF 2.9 3区 医学
Toxicology letters Pub Date : 2025-01-01 DOI: 10.1016/j.toxlet.2024.11.007
Rahul M. Nandre, Pramod S. Terse
{"title":"An overview of immunotoxicity in drug discovery and development","authors":"Rahul M. Nandre,&nbsp;Pramod S. Terse","doi":"10.1016/j.toxlet.2024.11.007","DOIUrl":"10.1016/j.toxlet.2024.11.007","url":null,"abstract":"<div><div>The immune system is one of the common targets of drugs’ toxicity (Immunotoxicity) and/or efficacy (Immunotherapy). Immunotoxicity leads to adverse effects on human health, which raises serious concerns for the regulatory agencies. Currently, immunotoxicity assessment is conducted using different <em>in vitro</em> and <em>in vivo</em> assays. <em>In silico</em> and <em>in vitro</em> human cell-based immunotoxicity assays should also be explored for screening purposes as these are time and cost effective as well as for ethical reasons. For <em>in vivo</em> studies, tier 1–3 assessments (Tier 1: hematology, serum globulin levels, lymphoid organ’s weight and histopathology; Tier 2: immunophenotyping, TDAR and cell mediated immunity; and Tier 3: host resistance) should be used. These non-clinical <em>in vivo</em> assessments are useful to select immunological endpoints for clinical trials as well as for precautionary labeling. As per regulatory guidelines, adverse immunogenicity information of drug should be included in product’s labeling to make health care practitioner aware of safety concerns before prescribing medicines and patient management (USFDA, 2022a, 2022b). This review mainly focuses on the importance of immunotoxicity assessment during drug discovery and development.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 66-75"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740791","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
In vitro assessment of the role of endoplasmic reticulum stress in sunitinib-induced liver and kidney toxicity 体外评估内质网应激在舒尼替尼诱导的肝和肾毒性中的作用
IF 2.9 3区 医学
Toxicology letters Pub Date : 2024-11-28 DOI: 10.1016/j.toxlet.2024.11.010
Ege Arzuk , Güliz Armağan
{"title":"In vitro assessment of the role of endoplasmic reticulum stress in sunitinib-induced liver and kidney toxicity","authors":"Ege Arzuk ,&nbsp;Güliz Armağan","doi":"10.1016/j.toxlet.2024.11.010","DOIUrl":"10.1016/j.toxlet.2024.11.010","url":null,"abstract":"<div><div>Sunitinib, a multi-targeted tyrosine kinase inhibitor, is prescribed for the treatment of metastatic gastrointestinal stromal tumors, advanced metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. Hepatotoxicity and nephrotoxicity are significant adverse effects of sunitinib administration; however, there is limited information regarding the molecular mechanisms of these adverse effects. The aim of the present study was to elucidate the role of endoplasmic reticulum stress in hepatotoxicity and nephrotoxicity induced by sunitinib. In addition to endoplasmic reticulum stress, oxidative stress and mitochondrial membrane potential were evaluated to investigate the molecular mechanism more comprehensively. Findings revealed that sunitinib exposure significantly increased the reactive oxygen species levels and decreased the Nrf2 gene expression and GSH/GSSG ratio, suggesting oxidative stress induction in normal hepatocyte (AML12) and normal kidney (HK-2) cell lines. Endoplasmic reticulum stress markers, including ATF4, CHOP, IRE1α, XBP1s and ATF6 mRNA expressions, were upregulated in AML12 cells. Furthermore, enhanced intracellular calcium levels also indicate endoplasmic reticulum stress in hepatocytes. In contrast, sunitinib exposure did not alter endoplasmic reticulum-related gene expression levels and intracellular calcium levels in HK-2 cells. In terms of mitochondrial membrane potential and caspase-3 activity, sunitinib induced mitochondrial membrane damage and increased caspase-3 activation not only in AML12 cells but also in HK-2 cells. The research findings indicate that sunitinib may induce cytotoxic effects in hepatocytes through mechanisms involving oxidative stress, endoplasmic reticulum stress, and mitochondrial damage. However, in the kidney, the toxicity mechanism is different from that of liver, and the endoplasmic reticulum stress does not seem to be involved in this mechanism.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 9-16"},"PeriodicalIF":2.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744124","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信