International Journal of Toxicology最新文献_第6页

Copper Chaperone Atox1 Protected the Cochlea From Cisplatin by Regulating the Copper Transport Family and Cell Cycle. 铜伴侣阿托x1通过调节铜转运家族和细胞周期保护耳蜗免受顺铂的侵害。

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-10-20 DOI: 10.1177/10915818231206665

Xubo Chen, Weiren Xiang, Lihua Li, Kai Xu

{"title":"Copper Chaperone Atox1 Protected the Cochlea From Cisplatin by Regulating the Copper Transport Family and Cell Cycle.","authors":"Xubo Chen, Weiren Xiang, Lihua Li, Kai Xu","doi":"10.1177/10915818231206665","DOIUrl":"10.1177/10915818231206665","url":null,"abstract":"Antioxidant 1 copper chaperone (Atox1) may contribute to preventing DDP cochlear damage by regulating copper transport family and cell cycle proteins. A rat model of cochlear damage was developed by placing gelatin sponges treated with DDP in the cochlea. HEI-OC1 cells were treated with 133 μM DDP as a cell model. DDP-induced ototoxicity in rats was confirmed by immunofluorescence (IF) imaging. The damage of DDP to HEI-OC1 cells was assessed by using CCK-8, TUNEL, and flow cytometry. The relationship between Atox1, a member of the copper transport protein family, and the damage to in vivo/vitro models was explored by qRT-PCR, western blot, CCK-8, TUNEL, and flow cytometry. DDP had toxic and other side effects causing cochlear damage and promoted HEI-OC1 cell apoptosis and cell cycle arrest. The over-expression of Atox1 (oe-Atox1) was accomplished by transfecting lentiviral vectors into in vitro/vivo models. We found that oe-Atox1 increased the levels of Atox1, copper transporter 1 (CTR1), and SOD3 in HEI-OC1 cells and decreased the expression levels of ATPase copper transporting α (ATP7A) and ATPase copper transporting β (ATP7B). In addition, the transfection of oe-Atox1 decreased cell apoptosis rate and the number of G2/M stage cells. Similarly, the expression of myosin VI and phalloidin of cochlea cells in vivo decreased. Atox1 ameliorated DDP-induced damage to HEI-OC1 cells or rats' cochlea by regulating the levels of members of the copper transport family.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Exacerbates Methamphetamine-Induced Activation of Microglia and Neuroinflammation. 髓细胞2缺乏触发受体表达加剧甲基苯丙胺诱导的小胶质细胞活化和神经炎症。

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-11-25 DOI: 10.1177/10915818231216397

Yanxia Peng, Genmeng Yang, Shangwen Wang, Wanrong Lin, Lihua Zhu, Wenjuan Dong, Baoyu Shen, Qianyun Nie, Shijun Hong, Lihua Li

{"title":"Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Exacerbates Methamphetamine-Induced Activation of Microglia and Neuroinflammation.","authors":"Yanxia Peng, Genmeng Yang, Shangwen Wang, Wanrong Lin, Lihua Zhu, Wenjuan Dong, Baoyu Shen, Qianyun Nie, Shijun Hong, Lihua Li","doi":"10.1177/10915818231216397","DOIUrl":"10.1177/10915818231216397","url":null,"abstract":"Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to neurotoxicity and drug addiction. Studies have shown that neurotoxicity is strongly associated with METH-induced neuroinflammation, and microglia are the key drivers of neuroinflammation. Triggering receptor expressed on myeloid cells 2 (TREM2) is reported to play a key role in activation of microglia and neuroinflammation. Yet, the molecular mechanisms by which METH causes neuroinflammation and neurotoxicity remain elusive. In the current study, we investigated the role of TREM2 in neuroinflammation induced by METH in BV2 cells and the wild-type (WT) C57BL/6J mice, CX3CR1GFP/+ transgenic mice, and TREM2 knockout (KO) mice. Postmortem samples from the frontal cortex of humans with a history of METH use were also analyzed to determine the levels of TREM2, TLR4, IBA1, and IL-1β. The expression levels of TREM2, TLR4, IBA1, IL-1β, iNOS, and Arg-1 were then assessed in the BV2 cells and frontal cortex of mice and human METH users. Results revealed that the expression levels of TREM2, TLR4, IBA1, and IL-1β were significantly elevated in METH-using individuals and BV2 cells. Microglia were clearly activated in the frontal cortex of WT C57BL/6 mice and CX3CR1GFP/+ transgenic mice, and the protein levels of IBA1, TREM2, TLR4, and IL-1β were elevated in the METH-induced mouse models. Moreover, TREM2-KO mice showed further increased microglial activation, neuroinflammation, and excitotoxicity induced by METH. Thus, these findings suggest that TREM2 may be a target for regulating METH-induced neuroinflammation.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138434038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A Retrospective Comparison of Electrocardiographic Parameters in Ketamine and Tiletamine-Zolazepam Anesthetized Indian Rhesus Monkeys (Macaca mulatta). 氯胺酮和利他敏-唑拉西泮麻醉印度恒河猴心电图参数的回顾性比较

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-12-18 DOI: 10.1177/10915818231221276

Laxit K Bhatt, Chitrang R Shah, Shital D Patel, Sudhir R Patel, Vipul A Patel, Rajesh J Patel, Nikita M Joshi, Niraj A Shah, Jitendra H Patel, Pankaj Dwivedi, Rajesh Sundar, Mukul R Jain

{"title":"A Retrospective Comparison of Electrocardiographic Parameters in Ketamine and Tiletamine-Zolazepam Anesthetized Indian Rhesus Monkeys (Macaca mulatta).","authors":"Laxit K Bhatt, Chitrang R Shah, Shital D Patel, Sudhir R Patel, Vipul A Patel, Rajesh J Patel, Nikita M Joshi, Niraj A Shah, Jitendra H Patel, Pankaj Dwivedi, Rajesh Sundar, Mukul R Jain","doi":"10.1177/10915818231221276","DOIUrl":"10.1177/10915818231221276","url":null,"abstract":"Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Safety Evaluation of a Prototypical Diazirine-Based Covalent Crosslinker and Molecular Adhesive. 一种典型重氮嘧啶基共价交联剂及分子胶粘剂的安全性评价。

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-11-21 DOI: 10.1177/10915818231215692

Miranda J Baran, Rebecca Hof, Angelique Groot, Irene Eurlings, Jet Gijsbrechts, Britt de Jong, Jeremy E Wulff

引用次数: 0

In Vitro Evaluation of Vancomycin-Induced Toxicity in Human Primary Knee Chondrocytes. 万古霉素对人膝关节原代软骨细胞毒性的体外评价。

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-11-21 DOI: 10.1177/10915818231216413

Susan Hall, Jane Grayson, Gary Grant, Christopher Vertullo, Shailendra Anoopkumar-Dukie

{"title":"In Vitro Evaluation of Vancomycin-Induced Toxicity in Human Primary Knee Chondrocytes.","authors":"Susan Hall, Jane Grayson, Gary Grant, Christopher Vertullo, Shailendra Anoopkumar-Dukie","doi":"10.1177/10915818231216413","DOIUrl":"10.1177/10915818231216413","url":null,"abstract":"Septic arthritis as a complication of orthopaedic joint surgery can have catastrophic outcomes for patients. To minimise infection risk associated with elective orthopaedics, topical vancomycin during surgery has become increasingly common. Evidence suggests that high concentrations of vancomycin, following direct application of the drug to the joint, are toxic towards various local cell types in the joint, including chondrocytes. However, the mechanism of this vancomycin tissue toxicity is yet to be determined. The aim of this study was to evaluate the toxicity of vancomycin on chondrocytes and the mechanisms of cell death involved. Human primary knee chondrocytes were exposed to vancomycin (1.25-10 mg/mL) for 24 h and their viability assessed using the resazurin reduction assay in vitro. Specific cell death mechanisms and their contributors, including reactive oxygen species (ROS) production and apoptosis, were measured. This study showed that high concentrations of vancomycin (5 and 10 mg/mL) were toxic towards human primary knee chondrocyte cells, while lower concentrations (1.25 and 2.5 mg/mL) were not. Cell death studies found that this occurred through an apoptotic pathway. This study provides additional support that vancomycin in high doses is toxic towards chondrocytes and preliminary evidence that this toxicity occurs via apoptotic cell death mechanisms.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A Commentary on Fasting of Nonclinical Research Animals. 关于非临床研究动物禁食的评论。

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-12-27 DOI: 10.1177/10915818231218975

David V Gauvin, Margaret McComb, Ryan Farero

{"title":"A Commentary on Fasting of Nonclinical Research Animals.","authors":"David V Gauvin, Margaret McComb, Ryan Farero","doi":"10.1177/10915818231218975","DOIUrl":"10.1177/10915818231218975","url":null,"abstract":"This commentary discusses the implementation of fasting in nonclinical animal experimental subjects. The short-term removal of food from cages of experimental animals is in all respects innocuous. The term \"stress\" is ill-defined and the statutes and regulations governing animal research laboratories that exert their authority in the performance of their operations do so without substantive grounds to base compliance. The legislative and administrative history of the implementation of the Animal Welfare Act (AWA) has evolved into the development of laboratory management strategies that focus on the reduction of the biological cost of stress to the animals and the determination of when subclinical stress (eustress) becomes distress. Animal welfare is based on the tenet that in laboratories conducting animal research in compliance with Good Laboratory Practices (Title 21 USC, Chapter 13,§58), it is the study protocol and the study director that establish procedures and processes that are approved by each Institutional Animal Care and Use Committee to ensure the humane care and use of animals in research, teaching, and testing and to ensure compliance with guidelines and regulations. This approval process establishes the justification of eustress in the environment that do not rise to the threshold of distress under the AWA.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Safety Assessment of Soy-Derived Ingredients as Used in Cosmetics. 化妆品中使用的大豆成分安全评估。

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-02-11 DOI: 10.1177/10915818241231249

Priya Cherian, Wilma F Bergfeld, Donald V Belsito, Curtis D Klaassen, Daniel C Liebler, James G Marks, Lisa A Peterson, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Ginkgo biloba-Derived Ingredients as Used in Cosmetics. 化妆品用银杏叶衍生成分的安全性评估。

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-02-01 Epub Date: 2023-11-06 DOI: 10.1177/10915818231210792

Christina L Burnett, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

{"title":"Safety Assessment of Ginkgo biloba-Derived Ingredients as Used in Cosmetics.","authors":"Christina L Burnett, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth","doi":"10.1177/10915818231210792","DOIUrl":"10.1177/10915818231210792","url":null,"abstract":"The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 10 Ginkgo biloba-derived ingredients, which are most frequently reported to function in cosmetics as skin conditioning agents or antioxidants. The Panel reviewed the available data to determine the safety of these ingredients. Because final product formulations may contain multiple botanicals, each containing the same constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. The Panel was concerned about the presence of ginkgolic acid in cosmetics. Industry should use good manufacturing practices to limit impurities. The Panel concluded that 5 Ginkgo biloba leaf-derived ingredients are safe in the present practices of use and concentration described in this safety assessment when formulated to be non-sensitizing; data are insufficient to determine the safety of the remaining 5 ingredients under the intended conditions of use in cosmetic formulations.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Safety Assessment of Adenosine as Used in Cosmetics. 化妆品中使用的腺苷安全性评估。

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-02-01 Epub Date: 2023-12-25 DOI: 10.1177/10915818231221790

Priya Cherian, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Butyrospermum parkii (Shea)-Derived Ingredients as Used in Cosmetics. 化妆品中使用的乳木果提取成分的安全性评估。

IF 2.2 4区医学

International Journal of Toxicology Pub Date : 2024-02-01 Epub Date: 2024-01-02 DOI: 10.1177/10915818231224230

Christina L Burnett, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0