Seyed Mobin Seyed Aliyan, Ali Roohbakhsh, Marzieh Jafari Fakhrabad, Zahar Salmasi, Mohammad Moshiri, Niosha Shahbazi, Leila Etemad
{"title":"Evaluating the Protective Effects of Thymoquinone on Methamphetamine-induced Toxicity in an <i>In Vitro</i> Model Based on Differentiated PC12 Cells.","authors":"Seyed Mobin Seyed Aliyan, Ali Roohbakhsh, Marzieh Jafari Fakhrabad, Zahar Salmasi, Mohammad Moshiri, Niosha Shahbazi, Leila Etemad","doi":"10.1177/02611929241237409","DOIUrl":"10.1177/02611929241237409","url":null,"abstract":"<p><p>Methamphetamine (Meth) is a highly addictive stimulant. Its potential neurotoxic effects are mediated through various mechanisms, including oxidative stress and the initiation of the apoptotic process. Thymoquinone (TQ), obtained from <i>Nigella sativa</i> seed oil, has extensive antioxidant and anti-apoptotic properties. This study aimed to investigate the potential protective effects of TQ against Meth-induced toxicity by using an <i>in vitro</i> model based on nerve growth factor-differentiated PC12 cells. Cell differentiation was assessed by detecting the presence of a neuronal marker with flow cytometry. The effects of Meth exposure were evaluated in the <i>in vitro</i> neuronal cell-based model via the determination of cell viability (in an MTT assay) and apoptosis (by annexin/propidium iodide staining). The generation of reactive oxygen species (ROS), as well as the levels of glutathione (GSH) and dopamine, were also determined. The model was used to determine the protective effects of 0.5, 1 and 2 μM TQ against Meth-induced toxicity (at 1 mM). The results showed that TQ reduced Meth-induced neurotoxicity, possibly through the inhibition of ROS generation and apoptosis, and by helping to maintain GSH and dopamine levels. Thus, the impact of TQ treatment on Meth-induced neurotoxicity could warrant further investigation.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"94-106"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040926","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}
{"title":"Editorial.","authors":"Judith C Madden","doi":"10.1177/02611929241232245","DOIUrl":"10.1177/02611929241232245","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"75-76"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704135","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}
Michael G Diemar, Mathieu Vinken, Marc Teunis, Cyrille A M Krul, Francois Busquet, Julia Dominika Zajac, Helena Kandarova, Raffaella Corvi, Matteo Z Rosso, Anastasiia Kharina, Louise Stab Bryndum, Michael Santillo, Denise Bloch, Olena Kucheryavenko, Demosthenes Panagiotakos, Vera Rogiers, Manon Beekhuijzen, Arianna Giusti, Abdulkarim Najjar, Carol Courage, Torben Koenig, Susanne Kolle, Harrie Boonen, Stephane Dhalluin, Julie Boberg, Boris P Müller, Predrag Kukic, Merel Ritskes-Hoitinga, Elena Grasselli, Tamara Zietek, Gilly Stoddart, Harm J Heusinkveld, Jose V Castell, Emilio Benfenati, Huan Yang, Simón Perera, Alicia Paini, Nynke I Kramer, Thomas Hartung, Manoe Janssen, Ellen Fritsche, Danyel G J Jennen, Matteo Piumatti, James Rathman, Jörg Marusczyk, Lucia Milec, Erwin L Roggen
{"title":"Report of the First ONTOX Stakeholder Network Meeting: Digging Under the Surface of ONTOX Together With the Stakeholders.","authors":"Michael G Diemar, Mathieu Vinken, Marc Teunis, Cyrille A M Krul, Francois Busquet, Julia Dominika Zajac, Helena Kandarova, Raffaella Corvi, Matteo Z Rosso, Anastasiia Kharina, Louise Stab Bryndum, Michael Santillo, Denise Bloch, Olena Kucheryavenko, Demosthenes Panagiotakos, Vera Rogiers, Manon Beekhuijzen, Arianna Giusti, Abdulkarim Najjar, Carol Courage, Torben Koenig, Susanne Kolle, Harrie Boonen, Stephane Dhalluin, Julie Boberg, Boris P Müller, Predrag Kukic, Merel Ritskes-Hoitinga, Elena Grasselli, Tamara Zietek, Gilly Stoddart, Harm J Heusinkveld, Jose V Castell, Emilio Benfenati, Huan Yang, Simón Perera, Alicia Paini, Nynke I Kramer, Thomas Hartung, Manoe Janssen, Ellen Fritsche, Danyel G J Jennen, Matteo Piumatti, James Rathman, Jörg Marusczyk, Lucia Milec, Erwin L Roggen","doi":"10.1177/02611929231225730","DOIUrl":"10.1177/02611929231225730","url":null,"abstract":"<p><p>The first Stakeholder Network Meeting of the EU Horizon 2020-funded ONTOX project was held on 13-14 March 2023, in Brussels, Belgium. The discussion centred around identifying specific challenges, barriers and drivers in relation to the implementation of non-animal new approach methodologies (NAMs) and probabilistic risk assessment (PRA), in order to help address the issues and rank them according to their associated level of difficulty. ONTOX aims to advance the assessment of chemical risk to humans, without the use of animal testing, by developing non-animal NAMs and PRA in line with 21st century toxicity testing principles. Stakeholder groups (regulatory authorities, companies, academia, non-governmental organisations) were identified and invited to participate in a meeting and a survey, by which their current position in relation to the implementation of NAMs and PRA was ascertained, as well as specific challenges and drivers highlighted. The survey analysis revealed areas of agreement and disagreement among stakeholders on topics such as capacity building, sustainability, regulatory acceptance, validation of adverse outcome pathways, acceptance of artificial intelligence (AI) in risk assessment, and guaranteeing consumer safety. The stakeholder network meeting resulted in the identification of barriers, drivers and specific challenges that need to be addressed. Breakout groups discussed topics such as hazard versus risk assessment, future reliance on AI and machine learning, regulatory requirements for industry and sustainability of the ONTOX Hub platform. The outputs from these discussions provided insights for overcoming barriers and leveraging drivers for implementing NAMs and PRA. It was concluded that there is a continued need for stakeholder engagement, including the organisation of a 'hackathon' to tackle challenges, to ensure the successful implementation of NAMs and PRA in chemical risk assessment.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"117-131"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485395","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}
{"title":"Thanks to Reviewers.","authors":"","doi":"10.1177/02611929241234014","DOIUrl":"https://doi.org/10.1177/02611929241234014","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"2611929241234014"},"PeriodicalIF":2.7,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742783","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}
{"title":"Toxicological Profiling of Potential Shikimate Kinase Inhibitors Against <i>Mycobacterium tuberculosis</i>.","authors":"Ashish Jhangiani, Vandana Panda, Aanchal Sukheja, Sneha Thomas, Piyush Dusseja, Siddhartha Pandya, Anand Chintakrindi","doi":"10.1177/02611929231217062","DOIUrl":"10.1177/02611929231217062","url":null,"abstract":"<p><p>Over the last decade, <i>Mycobacterium tuberculosis</i> has mutated into a putative 'superbug', as treatments against it have failed due to increasing antimicrobial resistance. As a result, the rising incidence of multidrug-resistant tuberculosis (MDR-TB) is posing a significant public health threat, thus, the need to develop effective drugs for MDR-TB has become an urgent priority. To identify new drug candidates for the treatment of MDR-TB, the present study was based on mycobacterial shikimate kinase (MtSK) as the pharmacological target. One hundred potential MtSK inhibitors were identified from literature and database searches to identify compounds that were designed to specifically function as MtSK antagonists. The ADME properties of these compounds were evaluated by using the SwissADME web tool. ProTox-II software was also used to investigate any potential endocrine disrupting effects, mediated through their interaction with oestrogenic and/or androgenic receptors. This study also aimed to predict LD<sub>50</sub> values of potential drug candidates that would be active against the standard H37Rv strain of <i>M. tuberculosis</i>, by using the ProTox-II <i>in silico</i> tool. The molecules for which no structural hazard alerts were identified with these software tools were further subjected to molecular docking analyses and molecular dynamic simulations to estimate their ability to interact with the MtSK enzyme. Preliminary results from SwissADME indicated that 30 molecules were drug-like, due to their physicochemical and pharmacokinetic properties. However, subsequent analysis with ToxTree and ProTox-II indicated that only three of these 30 drug-like molecules were suitable for taking forward into further <i>in vitro</i> experiments. This study, which is based on the use of commonly used open-source <i>in silico</i> tools, identified new MtSK ligands for potential use in the development of new drugs for the therapeutic management of tuberculosis. An initial prediction of their safety profile was also generated.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"10-27"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812059","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}
Ian Crooks, Julie Clements, Rodger Curren, Xiaoqing Guo, Michael Hollings, Mel Lloyd, Daniel Smart, David Thorne, Elisabeth Weber, Martha Moore
{"title":"Key Challenges for <i>In Vitro</i> Testing of Tobacco Products for Regulatory Applications: Recommendations for the <i>In Vitro</i> Mouse Lymphoma Assay.","authors":"Ian Crooks, Julie Clements, Rodger Curren, Xiaoqing Guo, Michael Hollings, Mel Lloyd, Daniel Smart, David Thorne, Elisabeth Weber, Martha Moore","doi":"10.1177/02611929231219153","DOIUrl":"10.1177/02611929231219153","url":null,"abstract":"<p><p>The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to develop recommendations for optimal scientific and technical approaches for conducting <i>in vitro</i> assays to assess potential toxicity within and across traditional tobacco and various tobacco and nicotine next-generation products (NGPs), including Heated Tobacco Products (HTPs) and Electronic Nicotine Delivery Systems (ENDS). This report was developed by a working group composed of attendees of the seventh IIVS workshop, 'Approaches and recommendations for conducting the mouse lymphoma gene mutation assay (MLA) and introduction to <i>in vitro</i> disease models', which was held virtually on 21-23 June 2022. This publication provides a background overview of the MLA, and includes the description of assay conduct and data interpretation, key challenges and recommended best practices for evaluating tobacco and nicotine products, with a focus on the evaluation of NGPs, and a summary of how the assay has been used to evaluate and compare tobacco and nicotine products.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"42-59"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500335","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}
{"title":"The Numbers of Animals Used in Mexico for Scientific and Educational Purposes.","authors":"Patricia Frías-Álvarez, Gustavo Ortiz-Millán","doi":"10.1177/02611929231217033","DOIUrl":"10.1177/02611929231217033","url":null,"abstract":"<p><p>In Mexico, there are no official public and reliably reported data on the total number and species of non-human animals used for scientific purposes. The aim of the current study was to calculate the total numbers of animals used for scientific and educational purposes in Mexico, from January 2015 to October 2021, based on data requested from the National Institute of Transparency, Access to Information and Protection of Personal Data (INAI, in Spanish). In this period, authorised laboratory animal facilities reported the use of 5,437,263 animals for scientific and educational purposes. However, these data should be viewed with caution, since there is no official register of all Mexican institutions that use animals for these purposes. The use of various species of different taxonomic groups was reported, including mammals, birds, reptiles, amphibians, fish and invertebrates. The main scientific purposes of this animal use were: technological development; innovation; laboratory testing; production of biologicals; quality control; diagnostic purposes; basic and applied research; and education. A robust system for the licensing and approval of animal use, as well as a means to ensure compliance with the relevant regulations, are both urgently required. In addition, in order to regulate animal use, monitor animal care and protect their welfare, the creation of a publicly accessible national database that records the number and species of the animals used is imperative.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"28-41"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138435446","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}