Differential eigengene network analysis reveals benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin consensus regulatory network in human liver cell line HepG2
In this study, we used transcriptomics data from the BaP- and TCCD-exposed human liver cell line HepG2, and performed differential eigengene network analysis to understand the correlation among genes and to untangle the common regulatory mechanism in the action of BaP and TCDD. The genes were grouped into 11 meta-modules with an overall preservation of 0.72 and were also segregated into three consensus time clusters: 12, 24, and 48 h. The analysis showed that the consensus genes in each time cluster were either directly regulated by the AHR or the AHR-TF interactions. Some TFs form a direct physical interaction with AHR su...
Source: Toxicology - February 4, 2024 Category: Toxicology Authors: Bojana Stanic Nata ša Sukur Nemanja Milo šević Jelena Markovic Filipovic Kristina Pogrmic-Majkic Nebojsa Andric Source Type: research
Development of a hierarchical support vector regression-based in silico model for the prediction of the cysteine depletion in DPRA
In this study, a quantitative structure-activity relationship (QSAR) model was developed using the innovative hierarchical support vector regression (HSVR) scheme. The aim was to quantitatively predict the potential for skin sensitization by analyzing the percent of cysteine depletion in Direct Peptide Reactivity Assay (DPRA). The results demonstrated accurate, consistent, and robust predictions in the training set, test set, and outlier set. Consequently, this model can be employed to estimate skin sensitization potential of novel or virtual compounds.PMID:38307191 | DOI:10.1016/j.tox.2024.153739 (Source: Toxicology)
Source: Toxicology - February 2, 2024 Category: Toxicology Authors: Giang H Ta Ching-Feng Weng Max K Leong Source Type: research
Deep Learning Algorithm Based on Molecular Fingerprint for Prediction of Drug-Induced Liver Injury
In this study, a high-quality dataset of 1573 compounds was assembled. The 48 classification models, which depended on six different molecular fingerprints, were built via deep neural network (DNN) and seven machine learning algorithms. Comparing the results of the DNN and machine learning models, the optional performing model was found as the one developed based on the DNN with ECFP_6 as input, which achieved the area under the receiver operating characteristic curve (AUC) of 0.713, balanced accuracy (BA) of 0.680, and F1 of 0.753. In addition, we used the SHapley Additive exPlanations (SHAP) algorithm to interpret the mo...
Source: Toxicology - February 2, 2024 Category: Toxicology Authors: Qiong Yang Shuwei Zhang Yan Li Source Type: research
Ochratoxin A stimulates release of IL-1 β, IL-18 and CXCL8 from cultured human microglia
Toxicology. 2024 Feb;502:153738. doi: 10.1016/j.tox.2024.153738. Epub 2024 Feb 1.ABSTRACTExposure to mycotoxins has been associated with the development of neuropsychiatric symptoms and Ochratoxin A (OTA) has emerged as one of the main mycotoxins associated with neurotoxicity. However, the mechanism via OTA exerts its neurotoxic effects is not well understood, especially the importance of activated microglia and their contribution to neuroinflammation. Here we report the effect of OTA on cultured immortalized human microglia-SV40, as compared to the effect of neurotensin (NT) and lipopolysaccharide (LPS) used as "positive"...
Source: Toxicology - February 1, 2024 Category: Toxicology Authors: Irene Tsilioni Theoharis C Theoharides Source Type: research
Silver nanoparticles induce endothelial cytotoxicity through ROS-mediated mitochondria-lysosome damage and autophagy perturbation: The protective role of N-acetylcysteine
This study may provide new evidence for the cardiovascular toxicity of AgNPs and serve as a reference for the safe use of nanoparticles(NPs) in the future.PMID:38290605 | DOI:10.1016/j.tox.2024.153734 (Source: Toxicology)
Source: Toxicology - January 30, 2024 Category: Toxicology Authors: Jing He Yunyun Ma Xudong Niu Jiansheng Pei Ru Yan Fangjing Xu Jing Ma Xiaojuan Ma Shaobin Jia Wanrui Ma Source Type: research
Exploring the dynamics of the ABCB1 membrane transporter P-glycoprotein in the presence of ATP and active/non-active compounds through molecular dynamics simulations
This study provides comprehensive insights into P-gp behavior with various ligands and ATP, offering implications for drug development, toxicity assessment and demonstrating the validity of the results derived from the MD simulations.PMID:38272384 | DOI:10.1016/j.tox.2024.153732 (Source: Toxicology)
Source: Toxicology - January 25, 2024 Category: Toxicology Authors: Liadys Mora Lagares Yunierkis P érez-Castillo Marjana Novi č Source Type: research
Dimethyl fumarate induces cardiac developmental toxicity in zebrafish via down-regulation of oxidative stress
This study provides a certain research basis for further study of DMF-induced cardiac developmental toxicity, and provides some experimental evidence for future clinical application and study of DMF.PMID:38272385 | DOI:10.1016/j.tox.2024.153735 (Source: Toxicology)
Source: Toxicology - January 25, 2024 Category: Toxicology Authors: Mengqi Wan Jiejun Liu Dou Yang Zhonghao Xiao Xue Li Jieping Liu Ling Huang Fasheng Liu Shouhua Zhang Qiang Tao Juhua Xiao Zigang Cao Source Type: research
Sex differences in 4-tert-octylphenol toxicokinetics: Exploration of sex as an effective covariate through an in vivo modeling approach
Toxicology. 2024 Feb;502:153733. doi: 10.1016/j.tox.2024.153733. Epub 2024 Jan 20.ABSTRACT4-tert-octylphenol (4-tert-OP) is a potentially harmful substance, which is found widely in the environment. Nevertheless, information on the in vivo toxicokinetics of 4-tert-OP is lacking, and quantitative risk assessment studies are urgently needed. Therefore, we aimed to quantitatively identify differences in the toxicokinetics of 4-tert-OP and its distribution among tissues between sexes. To this end, following exposure of male and female rats to 10 or 50 mg/kg 4-tert-OP orally and 4 or 8 mg/kg 4-tert-OP intravenously, we conducte...
Source: Toxicology - January 22, 2024 Category: Toxicology Authors: Seung-Hyun Jeong Ji-Hun Jang Hea-Young Cho Yong-Bok Lee Source Type: research
Exploring the multifaceted impact of lanthanides on physiological pathways in human breast cancer cells
This study delves into the mechanism by which calcium-like elements La and Ce inhibit breast cancer cell growth, shedding light on their interference in mitochondrial function, protein homeostasis, and cytoskeleton assembly.PMID:38253231 | DOI:10.1016/j.tox.2024.153731 (Source: Toxicology)
Source: Toxicology - January 22, 2024 Category: Toxicology Authors: Yi-Ming Huang Tsu-Yu Hsu Ching-Yu Liu Yu-Chen Hsieh Kuan-Yun Lai Ya-Wen Yang Kai-Yin Lo Source Type: research
Protective effects of vitamin E against acrylamide-induced hepatotoxicity and nephrotoxicity from fetal development to adulthood: Insights into Akt/NF- κB and Bcl-xL/Bax signaling pathways
This study aimed to investigate the mechanisms of oxidative stress, inflammation, and apoptosis that contribute to liver and kidney damage induced by chronic administration of ACR. Additionally, the effectiveness of vitamin E in mitigating these toxic effects was examined. The study initially involved dividing 40 pregnant rats into four groups. After lactation, the research continued with male offspring rats from each group. The offspring rats were divided into Control, Vitamin E, ACR, and ACR + Vitamin E groups. Following ACR administration, liver and kidney function tests were performed on serum samples. Biochemical anal...
Source: Toxicology - January 19, 2024 Category: Toxicology Authors: Nuray Üremi Ş Muhammed Mehdi Üremi Ş Mehmet G ül Eda Nur Özsoy Yusuf T ürköz Source Type: research
Autophagy alleviates hippocampal neuroinflammation by inhibiting the NLRP3 inflammasome in a juvenile rat model exposed particulate matter
Toxicology. 2024 Feb;502:153730. doi: 10.1016/j.tox.2024.153730. Epub 2024 Jan 17.ABSTRACTAmbient fine particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological diseases, which typically involve neuroinflammation. We investigated the impact of PM exposure on neuroinflammation using both in vivo (in a juvenile rat model with PM exposure concentrations of 1, 2, and 10 mg/kg for 28 days) and in vitro (in BV-2 and HT-22 cell models with PM concentrations of 50-200 μg/ml for 24 h). We observed that PM exposure induced the activation of the NLRP3 inflammasome, leadi...
Source: Toxicology - January 18, 2024 Category: Toxicology Authors: Jianxiong Gui Jie Liu Lingman Wang Xiaoyue Yang Bing Tian Hanyu Luo Dishu Huang Ziyao Han Jiaxin Yang Ran Ding Zhixu Fang Xue Li Li Cheng Li Jiang Source Type: research
Ferroptosis at the crossroads of manganese-induced neurotoxicity: A retrospective study
Toxicology. 2024 Feb;502:153727. doi: 10.1016/j.tox.2024.153727. Epub 2024 Jan 10.ABSTRACTManganese is an essential trace element, but overexposure can cause neurotoxicity and subsequent neurodegenerative diseases. Ferroptosis is a form of cell death characterized by lipid peroxidation and iron overload inside cells, which is closely related to manganese neurotoxicity. Manganese can induce ferroptosis through multiple pathways: causing oxidative stress and increased cellular reactive oxygen species (ROS), resulting in lipid peroxidation; depleting glutathione (GSH) and weakening the antioxidant capacity of cells; disruptin...
Source: Toxicology - January 12, 2024 Category: Toxicology Authors: Yaoyang Liu Shanyu Lv Guoguo He Changyong Wang Chaoyan Ou Source Type: research
Gut microbiota dysbiosis and intestinal barrier impairment in diarrhea caused by cold drink and high-fat diet
In conclusion, impaired gut microbial and mechanical barrier function is responsible for CDHFD-induced diarrhea. In this study, we constructed a model of diet-induced diarrhea by simulating human dietary patterns, evaluated the long-term effects of CDHFD on human intestinal barriers and immune systems, and revealed its mechanism of action based on chronic inflammation. This study validated the model's fit to provide an effective screening model for drug or functional food development.PMID:38216112 | DOI:10.1016/j.tox.2024.153728 (Source: Toxicology)
Source: Toxicology - January 12, 2024 Category: Toxicology Authors: Yajuan Tian Meng Fu Jie Su Meiqiu Yan Jingjing Yu Chenxing Wang Zhuangwei Niu Yuzhong Du Xueling Hu Jiayi Zheng Bai Tao Zengguang Gao Jianzhen Chen Suhong Chen Guiyuan Lv Source Type: research
Are the BPA analogues an alternative to classical BPA? Comparison between 2D and alternative 3D in vitro neuron model to assess cytotoxic and genotoxic effects
Toxicology. 2024 Feb;502:153715. doi: 10.1016/j.tox.2023.153715. Epub 2024 Jan 9.ABSTRACTBPA is used in a wide range of consumer products with very concern toxicological properties. The European Union has restricted its use to protect human health. Industry has substituted BPA by BPA analogues. However, there is a lack of knowledge about their impacts. In this work, BPA and 5 BPA analogues (BPS, BPAP, BPAF, BPFL and BPC) have been studied in classical SH-SY5Y and the alternative 3D in vitro models after 24 and 96 h of exposure. Cell viability, percentage of ROS, cell cycle phases as well as the morphology of the spheroids ...
Source: Toxicology - January 11, 2024 Category: Toxicology Authors: Marta Sendra M ónica Cavia-Saiz Pilar M úñiz Source Type: research
Mechanism of cadmium-induced nephrotoxicity
Toxicology. 2024 Feb;502:153726. doi: 10.1016/j.tox.2024.153726. Epub 2024 Jan 6.ABSTRACTHeavy metals are found naturally in our environment and have many uses and applications in daily life. However, high concentrations of metals may be a result of pollution due to industrialization. In particular, cadmium (Cd), a white metal abundantly distributed in the terrestrial crust, is found in mines together with zinc, which accumulates after volcanic eruption or is found naturally in the sea and earth. High levels of Cd have been associated with disease. In the human body, Cd accumulates in two ways: via inhalation or consumptio...
Source: Toxicology - January 8, 2024 Category: Toxicology Authors: Claudia J Bautista Nidia Arango Consuelo Plata Irma B Mitre-Aguilar Joyce Trujillo Victoria Ram írez Source Type: research
